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Background: Hematopoietic cell transplantation (HCT) increases survival for acute leukemia. Outpatient allogeneic HCT reduces costs and increases transplant rates in developing countries. We report outcomes of outpatient HLA-identical and haploidentical HCT in acute leukemia. Methods: This single-center retrospective cohort study analyzed 121 adult patients with acute myeloblastic (AML) and acute lymphoblastic leukemia (ALL) receiving an outpatient allogeneic HCT with peripheral blood allografts after reduced-intensity conditioning (RIC) from 2012-2022. Results: There were 81 (67%) haploidentical and 40 (33%) HLA-identical transplants. Complete chimerism (CC) at day +100 was not different in HLA-identical compared to haploidentical HCT (32.5% and 38.2%, P=0.054). Post-HCT complications, including neutropenic fever (59.3% vs. 40%), acute graft-versus-host-disease (aGVHD) (46.9% vs. 25%), cytokine release syndrome (CRS) (18.5% vs. 2.5%), and hospitalization (71.6% vs 42.5%) were significantly more frequent in haploidentical HCT. Two-year overall survival (OS) was 60.6% vs. 46.9%, (P=0.464) for HLA-identical and haplo-HCT, respectively. There was no difference in the 2-year disease-free-survival (DFS) (33.3% vs. 35%, P=0.924) between transplant types. In multivariate analysis, positive measurable residual disease (MRD) at 30 days (HR 8.8, P=0.018) and 100 days (HR 28.5, P=0.022) was associated with lower OS, but not with non-relapse mortality (NRM) (P=0.252 and P=0.123, univariate). In univariate analysis, both 30-day and 100-day MRD were associated with lower DFS rates (P=0.026 and P=0.006), but only day 30 MRD was significant in multivariate analysis (P=0.050). In the case of relapse, only MRD at day 100 was associated with increased risk in the univariate and multivariate analyses (HR 4.48, P=0.003 and HR 4.67, P=0.008). Chronic graft-versus-host-disease (cGVHD) was protective for NRM (HR 0.38, P=0.015). There was no difference in cumulative incidence of relapse (CIR) between transplant types (P=0.126). Forty-four (36.4%) patients died, with no difference between HCT type (P=0.307). Septic shock was the most frequent cause of death with 17 cases, with no difference between transplant types Conclusions: Outpatient peripheral blood allogenic HCT after RIC is a valid and effective alternative for adult patients suffering acute myeloblastic or lymphoblastic leukemia in low-income populations. [ABSTRACT FROM AUTHOR]

BackgroundHematopoietic cell transplantation (HCT) increases survival for acute leukemia. Outpatient allogeneic HCT reduces costs and increases transplant rates in developing countries. We report outcomes of outpatient HLA-identical and haploidentical HCT in acute leukemia.MethodsThis single-center retrospective cohort study analyzed 121 adult patients with acute myeloblastic (AML) and acute lymphoblastic leukemia (ALL) receiving an outpatient allogeneic HCT with peripheral blood allografts after reduced-intensity conditioning (RIC) from 2012-2022.ResultsThere were 81 (67%) haploidentical and 40 (33%) HLA-identical transplants. Complete chimerism (CC) at day +100 was not different in HLA-identical compared to haploidentical HCT (32.5% and 38.2%, P=0.054). Post-HCT complications, including neutropenic fever (59.3% vs. 40%), acute graft-versus-host-disease (aGVHD) (46.9% vs. 25%), cytokine release syndrome (CRS) (18.5% vs. 2.5%), and hospitalization (71.6% vs 42.5%) were significantly more frequent in haploidentical HCT. Two-year overall survival (OS) was 60.6% vs. 46.9%, (P=0.464) for HLA-identical and haplo-HCT, respectively. There was no difference in the 2-year disease-free-survival (DFS) (33.3% vs. 35%, P=0.924) between transplant types. In multivariate analysis, positive measurable residual disease (MRD) at 30 days (HR 8.8, P=0.018) and 100 days (HR 28.5, P=0.022) was associated with lower OS, but not with non-relapse mortality (NRM) (P=0.252 and P=0.123, univariate). In univariate analysis, both 30-day and 100-day MRD were associated with lower DFS rates (P=0.026 and P=0.006), but only day 30 MRD was significant in multivariate analysis (P=0.050). In the case of relapse, only MRD at day 100 was associated with increased risk in the univariate and multivariate analyses (HR 4.48, P=0.003 and HR 4.67, P=0.008). Chronic graft-versus-host-disease (cGVHD) was protective for NRM (HR 0.38, P=0.015). There was no difference in cumulative incidence of relapse (CIR) between transplant types (P=0.126). Forty-four (36.4%) patients died, with no difference between HCT type (P=0.307). Septic shock was the most frequent cause of death with 17 cases, with no difference between transplant typesConclusionsOutpatient peripheral blood allogenic HCT after RIC is a valid and effective alternative for adult patients suffering acute myeloblastic or lymphoblastic leukemia in low-income populations.

Background/aim: To analyze the long-term outcome of pediatric patients with acute myeloblastic leukemia. Materials and methods: Data from 69 patients 0--18 years of age diagnosed between December 2001 and October 2019 were analyzed in April 2023. Patients received MRC-AML10 chemotherapy (2ADE+MACE+MidAC). No maintenance chemotherapy or preventive cranial radiotherapy was administered. Twelve patients with Down syndrome and 15 patients with promyelocytic leukemia were in the cohort. Patients with Down syndrome received reduced chemotherapy (cumulative anthracycline 420 mg/m2, cytarabine 3.4 g/m2, etoposide 1400 mg/m2). ATRA was added to chemotherapy in promyelocytic leukemia. Results: Four patients (5.8%) died in the induction (two typhlitis, one intracranial hemorrhage, and one resistant disease). The complete remission rate of 66 patients was 87.8%. There was one death due to cardiotoxicity. Total infection-related deaths were 7.2%. Seven patients with high-risk criteria and one with resistant disease underwent hematopoietic stem cell transplantation (HSCT) following the first-line treatment. All seven patients in remission were alive and disease-free. The relapse rate was 34.4% (n = 21). Four patients developing marrow relapse were disease-free in the second remission after salvage and maintenance chemotherapy. Thirteen patients (18.84%) underwent HSCT in the second remission and 8 are alive and disease-free. The mean follow-up period of patients from diagnosis was 185 ± 13 months. Thirty-four patients (49.2%) were alive and disease-free in the first remission whereas another two patients in the first remission developed secondary malignancy. In good, standard, and poor risk groups, event-free survival (EFS) rates were 68.2%, 52.9%, and 10%, and overall survival (OS) rates were 86.4%, 79.4%, and 20%, respectively. Fifteen years of EFS and OS of the whole cohort were 49.3% and 69.6%, respectively. Conclusion: When compared with national data and multicenter studies of developed countries, survival rates were acceptable. [ABSTRACT FROM AUTHOR]

Simple Summary: Post-transfusion iron overload is a common side effect of anticancer treatment, including leukemias. We showed that serum ferritin levels could be valuable prognostic marker of death in children with AML and ALL. Importantly, improved survival of leukemia patients was found to be associated with lower ferritin values before therapy. It is noteworthy that the observed phenomenon was dependent on the cancer type, sex, and age of the studied patients. Transfusions of packed red blood cells (PRBCs), given due to an oncological disease and its acute complications, are an indispensable part of anticancer therapy. However, they can lead to post-transfusion iron overload. The study aim was to evaluate the role of ferritin as a nonspecific marker of leukemic growth and marker of transfusion-related iron overload. We performed a longitudinal study of PRBC transfusions and changes in ferritin concentrations during the oncological treatment of 135 patients with childhood acute lymphoblastic and acute myeloblastic leukemia (ALL and AML, median age 5.62 years). At the diagnosis, 41% of patients had a ferritin level over 500 ng/mL, and 14% of patients had a ferritin level over 1000 ng/mL. At the cessation of the treatment, 80% of the children had serum ferritin (SF) over 500 ng/mL, and 31% had SF over 1000 ng/mL. There was no significant difference between SF at the beginning of the treatment between ALL and AML patients, but children with AML finished treatment with statistically higher SF. AML patients had also statistically higher number of transfusions. We found statistically significant positive correlations between ferritin and age, and weight and units of transfused blood. Serum ferritin at the moment of diagnosis can be a useful marker of leukemic growth, but high levels of SF are connected with iron overload in both AML and ALL. [ABSTRACT FROM AUTHOR]

This single-center retrospective study was performed to evaluate the safety and efficacy of FMS-like tyrosine kinase 3 (FLT3) inhibitors before and after allogeneic hematopoietic cell transplantation (HCT) in relapsed/refractory patients with FLT3-mutation positive acute myeloid leukemia (AML). Ten patients who met the eligibility criteria were included. Eight of them achieved hematological remission at HCT, within a median span of 79 days (range: 43–197). In post-HCT, patients started maintenance therapy (MT; median time-to-start 79 days, range: 43–197), and the median duration of MT was 390 days (range: 67–815). Grade 3 hematological adverse events (AEs) were found in two patients, and non-hematological AEs were found in five patients. Nine patients underwent either dose reduction, discontinuation of therapy, or a switch to another FLT3 inhibitor due to AEs. Disease relapse occurred in one patient during MT. At the time of the last follow-up, seven patients are alive and disease-free, while three have died due to infection or transplant complications. In relapsed/refractory FLT3 mutation-positive AML, the use of FLT3 inhibitors can lead to high response rates and provide a safe bridge from HCT to MT. If sufficient attention is paid to safety, this therapy is expected to prevent disease relapse even with reduced dosages. [ABSTRACT FROM AUTHOR]

Sweet syndrome, also called acute febrile neutrophilic dermatosis, is a rare disorder characterized by skin lesions accompanied by high fever and elevated inflammatory markers.

ABSTRACTObjectives and Methods This single-center retrospective study was performed to evaluate the safety and efficacy of FMS-like tyrosine kinase 3 (FLT3) inhibitors before and after allogeneic hematopoietic cell transplantation (HCT) in relapsed/refractory patients with FLT3-mutation positive acute myeloid leukemia (AML).Results Ten patients who met the eligibility criteria were included. Eight of them achieved hematological remission at HCT, within a median span of 79 days (range: 43–197). In post-HCT, patients started maintenance therapy (MT; median time-to-start 79 days, range: 43–197), and the median duration of MT was 390 days (range: 67–815). Grade 3 hematological adverse events (AEs) were found in two patients, and non-hematological AEs were found in five patients. Nine patients underwent either dose reduction, discontinuation of therapy, or a switch to another FLT3 inhibitor due to AEs. Disease relapse occurred in one patient during MT. At the time of the last follow-up, seven patients are alive and disease-free, while three have died due to infection or transplant complications.Conclusion In relapsed/refractory FLT3 mutation-positive AML, the use of FLT3 inhibitors can lead to high response rates and provide a safe bridge from HCT to MT. If sufficient attention is paid to safety, this therapy is expected to prevent disease relapse even with reduced dosages.

Introduction: Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage. Methods: In our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN). Results and discussion: Overall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening. [ABSTRACT FROM AUTHOR]

IntroductionNeutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage. MethodsIn our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN). Results and discussionOverall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening.

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A 58-year-old woman presented with acute myeloblastic leukemia (AML) developed a bilateral dendritic epithelial keratitis without retinitis. The patient was initially treated with oral acyclovir with a possible diagnosis of herpes simplex virus (HSV) keratitis. Polymerase chain reaction (PCR) was performed on ocular discharge specimens collected by soft-tipped applicators reported as cytomegalovirus (CMV). Then, acyclovir was discontinued and bilateral CMV keratitis was treated with IV ganciclovir and her epithelial lesions gradually disappeared. The current case report confirms that CMV is capable of generating corneal epithelial engagement without retina involvement and demonstrated that CMV keratitis is an emergent problem of AML. Therefore, in any case with bilateral corneal herpes keratitis, the patient should be evaluated for immune system deficiency.

Simple Summary: Acute myeloid leukemia is the most common type of acute leukemia in adults. It is associated with poor outcomes, especially in older patients. Treatments based exclusively on chemotherapy do not achieve high overall survival rates, or in any case, only in a small group of patients. The objective of this review is to discuss the treatment of acute myeloid leukemia from newly approved therapeutic drugs to newer strategies. In first line, the combination of new targeted therapies with standard chemotherapy achieves better outcomes in "fit" patients. For "unfit" patients the combination of different targeted therapies provides them with better overall survival rates, with limited toxicity. As for refractory and relapsed acute myeloid leukemia, development of immunotherapy or new targeted therapies brings new hope. Acute myeloid leukemia is a heterogeneous disease defined by a large spectrum of genetic aberrations that are potential therapeutic targets. New targeted therapies have changed the landscape for a disease with poor outcomes. They are more effective than standard chemotherapy with a good safety profile. For "fit patients" in first-line, the combination of gemtuzumab ozogamicin or midostaurin with intensive chemotherapy or Vyxeos is now considered the "standard of care" for selected patients. On the other hand, for "unfit patients", azacitidine-venetoclax has been consolidated as a frontline treatment, while other combinations with magrolimab or ivosidenib are in development. Nevertheless, global survival results, especially in relapsed or refractory patients, remain unfavorable. New immunotherapies or targeted therapies, such as Menin inhibitors or sabatolimab, represent an opportunity in this situation. Future directions will probably come from combinations of different targeted therapies ("triplets") and maintenance strategies guided by measurable residual disease. [ABSTRACT FROM AUTHOR]

IntroductionOver the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010–2017.MethodsThe Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population

Chronic subdural hematoma, a common neurosurgical disease, is mostly caused by craniocerebral trauma. Chronic subdural hematoma caused by acute myeloblastic leukemia is rarely reported, and its pathogenesis and strategies for clinical treatment remain controversial. Here, we report a rare case of chronic subdural hematoma caused by acute myeloblastic leukemia. The patient's condition deteriorated quickly after admission, and emergency trepanation and drainage of the chronic subdural hematoma was performed, followed by oral administration of atorvastatin. The platelet levels continued to decrease during neurosurgical treatment. Bone marrow cytology, flow cytology, and karyotype analysis suggested acute myelocytic leukemia (AML). Then, the patient was transferred to the hematology department for chemotherapy treatment, during which there was no recurrence of hematoma. Chronic subdural hematoma caused by acute myeloblastic leukemia is a very rare disease. Surgery should be performed when the intracranial hematoma is more than 10mm thick and the midline structures are displaced by more than 5mm, and postoperative treatment should be supplemented with atorvastatin to prevent recurrence. Chemotherapy should be given promptly to treat leukemia after stabilization of neurological conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Xeroderma pigmentosum is a rare inherited disease characterized by extreme hypersensitivity to ultraviolet rays and predisposing to cutaneous malignancies that can appear in childhood. These manifestations are often associated with ocular lesions and sometimes with neurological disorders. The association of xeroderma pigmentosum with internal neoplasms such as acute myeloblastic leukemia is not reported with great frequency, which confirms the rarity of this occurrence. Case report A 26-year-old Moroccan women, xeroderma pigmentosum patient, was diagnosed with acute myeloblastic leukemia with a complex karyotype. Due to the adverse risk of the xeroderma pigmentosum association with acute myeloblastic leukemia and the profile of acute myeloblastic leukemia with complex karyotype and monosomy 7, which constitute factors of poor prognosis, as well as the absence of studies conceding the tolerance of the chemotherapy by patients suffering from xeroderma pigmentosum, our patient was put under low-dose cytarabine protocol with granulocyte colony-stimulating factor. Unfortunately, she died on the tenth day of chemotherapy by acute pulmonary edema of cardiogenic pace complicated by tamponade. Conclusion According to reports, it is the second case showing association of xeroderma pigmentosum with acute myeloblastic leukemia. The management of these patients remains a challenge. Studies focusing on xeroderma pigmentosum patients developing hematological malignancies are necessary to better understand the most appropriate strategies and precautions for this specific case.

Acute myeloid leukemia (AML) is a quickly aggressive hematopoietic disorder that progress due to the accumulation and clonal expansion of immature myeloid cells. Despite the latest developments in AML treatment, repeated relapses and drug resistance remain one of the major challenges in treatment of leukemia. Currently, it is well known that the components of the tumor microenvironment such as cellular and non-cellular elements play a critical function in treatment failures of AML, also they are most common cause of complications including suppression of hematopoiesis. Exosomes are membrane-bound extracellular vesicles (EVs) that transfer signaling molecules and have attracted a large amount of attention due to their important role in inter-cellular communication in health and disease. Exosomes participate in the survival and chemoresistance of many leukemia through transferring their rich cargos of molecules including miRNAs, growth factors, and cytokines. The key producers of exosomes that mainly participate to AML pathogenesis are bone marrow mesenchymal stem cell (BMSCs) and AML cell themselves. These cells release an enormous number of exosomes that affect several target cells such as natural killer (NK) and hematopoietic stem cells to the development of leukemia proliferation and progression. In the present study, a comprehensive review of the literature has been done to briefly discuss the biology of exosomes and highlight the role of exosomes derived from AML in the progress of acute myeloid leukemia.

A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson’s disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient’s condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.

Background. Curaxin CBL0137 is a novel non-genotoxic compound with anti-cancer activity based on CBL0137 ability of non-covalent interaction with DNA causing histone chaperone FACT relocation. Anti-cancer activity of this drug was demonstrated previously on the wide panel of solid cancer models in vitro and in vivo.Objectives. Estimation of anticancer effects of CBL0137 on the acute myeloblastic leukemia cells (THP-1) and acute lymphoblastic leukemia (CCRF-CEM).Materials and methods. CBL0137 cytotoxicity was analyzed using the MTT test, the effects on the cell cycle and the induction of apoptosis was assessed by flow cytometry, the activity of signaling pathways in cells treated with CBL0137 was determined by real-time polymerase chain reaction.Results. Cell treatment with CBL0137 led to cell cycle arrest and apoptosis induction. In the study of CBL0137 effect on target gene clusters of 10 signal transduction pathways involved in the pathogenesis of acute leukemia we have showed that CBL0137 inhibited the expression of down-stream genes of WNT and Hedgehog signaling in both cell lines. In THP-1 cells we also observed the inhibition of the expression of PPARγ target and hypoxia-activated genes. In CCRF-CEM cells CBL0137 also induced the expression of Notch signaling target genes.Conclusion. The antitumor activity of CBL0137 was demonstrated on acute leukemia cell cultures, the drug possesses cytotoxicity, causes cell cycle arrest and activation of apoptosis. Significant changes in the expression of efferent gene clusters of several signaling pathways were observed in the cells treated with CBL0137.

The article presents a study on the distribution of gene polymorphisms in the histocompatibility antigens among the patients diagnosed with AML, and healthy donors in the Republic of Kazakhstan, as well as features of the HLA-A*, *B, Cw*, DRB1*, DQB1* distribution among the patients with acute myeloid leukemia (AML). HLA typing and data processing were performed at the Research and Production Center of Transfusiology, Nur-Sultan. A total of 3808 people were examined, including 3621 healthy blood donors and 187 patients diagnosed with AML. Genomic DNA for HLA typing was isolated from peripheral blood leukocytes by proteinase method using columns with silica membrane and using a set of reagents PROTRANS DNA BOX (Protrans, Germany). Typing of HLA-A, B, C, DRB1, DQB1 in the patients and blood donors was performed by polymerase chain reaction using commercial reagent kits from Protrans (PROTRANS HLA- A*/B*/DRB1* Cyclerplate System, PROTRANS HLA-C* Cyclerplate System, PROTRANS HLA-DQB1* Cyclerplate System).HLA-A*31 (OR = 1.8; CI 1.16-2.79; p < 0.01) proved to be more common in the group of patients compared to the control group, which suggesting an association between AML and presence of this antigen. The control group showed an increased frequency of HLA-A*02 antigen (OR = 0.55; CI 0.41-0.75; p < 0.01). This antigen may be, therefore, exert a protective effect in AML development.The studies of major histocompatibility complex which include HLA genes, did significantly expanded the understanding of HLA antigens which may have strong associative links with distinct diseases, and moderately or poorly expressed links in other disorders. Analysis of the literature data showed that myeloid leukemia is characterized by decreased frequency of HLA-B13, B14, B40 antigens, most often determined by antigens B16, Bw 22, B27. In this study, HLA-A*31, B*37 were associated with AML. Phenotypes with antigens HLA-A*02, B*27, C*02, DRB1*01, *04, DQB1*06 have a probable protective effect on the development of this pathology.The study has determined some features of histocompatibility gene distribution in AML patients, detection of HLA-markers that determine the risk or resistance to the occurrence of this disease. We have established characteristic specific markers of HLA system among AML patients in Kazakhstan, which may be associated with higher risk of the disease.

Despite their small size, the membrane-bound particles named extracellular vesicles (EVs) seem to play an enormous role in the pathogenesis of acute leukemia. From oncogenic hematopoietic stem cells (HSCs) to become leukemic cells to alter the architecture of bone marrow (BM) microenvironment, EVs are critical components of leukemia development. As a carrier of essential molecules, especially a group of small non-coding RNAs known as miRNA, recently, EVs have attracted tremendous attention as a prognostic factor. Given the importance of miRNAs in the early stages of leukemogenesis and also their critical parts in the development of drug-resistant phenotype, it seems that the importance of EVs in the development of leukemia is more than what is expected. To be familiar with the clinical value of leukemia-derived EVs, this review aimed to briefly shed light on the biology of EVs and to discuss the role of EV-derived miRNAs in the development of acute myeloid leukemia and acute lymphoblastic leukemia. By elaborating the advances and challenges concerning the isolation of EVs, we discuss whether EVs could have a prognostic value in the clinical setting for leukemia.

Background: Xeroderma pigmentosum is a rare inherited disease characterized by extreme hypersensitivity to ultraviolet rays and predisposing to cutaneous malignancies that can appear in childhood. These manifestations are often associated with ocular lesions and sometimes with neurological disorders. The association of xeroderma pigmentosum with internal neoplasms such as acute myeloblastic leukemia is not reported with great frequency, which confirms the rarity of this occurrence.Case Report: A 26-year-old Moroccan women, xeroderma pigmentosum patient, was diagnosed with acute myeloblastic leukemia with a complex karyotype. Due to the adverse risk of the xeroderma pigmentosum association with acute myeloblastic leukemia and the profile of acute myeloblastic leukemia with complex karyotype and monosomy 7, which constitute factors of poor prognosis, as well as the absence of studies conceding the tolerance of the chemotherapy by patients suffering from xeroderma pigmentosum, our patient was put under low-dose cytarabine protocol with granulocyte colony-stimulating factor. Unfortunately, she died on the tenth day of chemotherapy by acute pulmonary edema of cardiogenic pace complicated by tamponade.Conclusion: According to reports, it is the second case showing association of xeroderma pigmentosum with acute myeloblastic leukemia. The management of these patients remains a challenge. Studies focusing on xeroderma pigmentosum patients developing hematological malignancies are necessary to better understand the most appropriate strategies and precautions for this specific case. [ABSTRACT FROM AUTHOR]

Objective: Natural killers (NK) cell function is mainly controlled by the expression of killer immunoglobulin-like receptors (KIRs) and their ligation with the corresponding ligands. The objective of this study was to investigate the putative association of KIRs, HLA class I ligands, and KIR/ligand combinations with rates of development of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Materials and Methods: The KIR/HLA I genotypes of 82 patients with leukemia (ALL, n=52; AML, n=17; and CML, n=13) were determined by PCR-SSP method and compared with genotypes of healthy controls (n=126). Results: KIR genotype frequency differed significantly between myelogenous leukemia patients and healthy controls for KIR2DL5A (17.6% vs. 47.7%, p=0.02), KIR3DS1 (17.6% vs. 47.6%, p=0.02), and KIR2DS4*001 (36.6% vs. 20.2%, p=0.017). The incidence of homozygous HLA-BBw4 (31.0% vs. 12.5%, p=0.042) and HLABw4Thr80 Thr80 (13.0% vs. 1.2%, p=0.01) was significantly elevated in myeloid leukemia patients compared to healthy controls. KIR/HLA class I ligand profile KIR3DS1(+)/L (-) was decreased and KIR3DL2(+)/ HLA-A3/11(-) was increased among myeloid leukemia cases compared to controls. Conclusion: These data suggest that the activity of NK cells as determined by inherited KIR/HLA class I ligand polymorphisms influences the susceptibility to myelogenous leukemia, but not to lymphoblastic leukemia. Additionally, the KIR genotype characterized by the absence of the inhibitory KIR2DL2 and the activating KIR2DS2 and KIR2DS3 (ID2) was found at a lower frequency in patients compared to controls, which confirmed the need for complex analysis based on all possible KIR/HLA class I ligand polymorphism combinations.

Objective: To determine and describe the clinical manifestations and hematological profiles of pediatric Acute Myeloblastic Leukemia (AML) in Dr. Hasan Sadikin General Hospital (RSHS), Bandung as a tertiary hospital in West Java, Indonesia. Methods: A retrospective cross-sectional study using the total sampling method was performed on the medical records of pediatric patients (0-18 years old)who were diagnosed as AML for the first time through bone marrow examination during the period of January 1, 2015 – December 31, 2017. Results: Of the 54 subjects who met the inclusion criteria, 42.6% were AML patients in the age group 6-12 years with male patients comprised 59.3% of the total number of subjects. Patients generally experienced pallor (83.3%), fever (75.9%), and decreased appetite (70.4%). The hematological profiles showed that 35.2% of patients had Hb 50,000 cells/mm3. The majority of the subjects had a platelet count of 50% (46.3%). Conclusion: Clinical manifestations and hematological profiles are important to diagnose AML, especially in pediatric patients. By assessing the manifestations and profiles, it is feasible to access and detect suspected cases of AML.

BACKGROUND: Acute myeloblastic leukemia is the most common acute leukemia in adults, with both diagnostic and therapeutic challenges. It has a poor treatment outcome both locally and internationally. The aim of this study was to investigate some epidemiological aspects and treatment outcome of AML patients treated in single center. PATIENTS AND METHODS: A retrospective observational study extended from February 2013 to February 2018 and included 98 patients who referred to Hiwa Hematology Oncology Hospital in Sulaymaniyah city. All patients had met the diagnostic criteria by flow cytometry for de novo acute myeloid leukemia (AML). Electronic records of all patients were reviewed carefully. RESULTS: Ninety-eight patients (46 females and 52 males) with a mean age of 42 years were included the study, with new diagnosis of AML, most of the patients were below the age of 60 years (81%), while only 19% were 60 years of age or older. The most frequent subtype is AML M3 (n = 25; 25.5%) of patients, followed by M1, M2 (n = 16; 16.3%) each, and M5 (n = 15; 15.3%) with M4, M0, M6, M7, and acute leukemia of ambiguous lineage comprising the remainder, respectively. The clinical features at the diagnosis of the 98 patients included pallor in 91 patients (92.9%), easy fatigability in 82 patients (83.6%), while bleeding tendency was present in 46 patients (46.9%) in the form of ecchymosis, petechial hemorrhage, epistaxis, or abnormal vaginal bleeding. Fever was present in 85 patients (86.7%), while pain in the form of headache, generalized body ache, or bone pain was initially manifested in 29 patients (29.6%). The survival of our patients at 1 year is (88%) M3 patients, while it was (58%) for non-M3 patient. CONCLUSIONS: Clinical and epidemiological characteristics were different in some aspect, while comparable in other when compared to published studies. treatment outcome and survival data were comparable to international data.

The ABO system is an essential blood group in clinical transfusion medicine implicated in several human diseases. The ABO system has been investigated for over a century, with various studies exploring potential links to disease susceptibility. The study examines the possible relationship between leukemia and the distribution and the ABO blood group system discrepancy. A comprehensive review was conducted on the recommended databases to review the ABO blood groups, their association with leukemia, and the expected changes in blood groups among leukemia patients. The study highlights different kinds of leukemia, such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL), their characteristics, and their relationship with ABO blood groups. The document concludes that studying ABO blood group distributions among leukemia patients showed that the most common blood group in acute leukemia is the A group, while in chronic leukemia, the O group is predominant; more studies are required. This study also confirmed an association between leukemia and ABO blood group discrepancy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Elzein et al.)

In patients with hematologic malignancies, acute kidney injury (AKI) is the most common kidney complication requiring nephrologist consultation. Although the causes of AKI are multifactorial, primary tumor infiltration is rare in patients with acute myeloblastic leukemia (AML). This makes it challenging to determine the cause of AKI and the optimal chemotherapy regimen for AML. We describe two cases of AML (French-American-British classification: M2, M4) in patients with AKI requiring hemodialysis. We successfully identified the cause of AKI as primary leukemic infiltration and started induction chemotherapy in the setting of hemodialysis. This treatment significantly improved renal function and resulted in AML remission. In this report, we describe several clinical characteristics of AKI due to primary tumor infiltration. In addition, we emphasize the importance of onconephrology, a new subspecialty concerned with the complex relationship between the kidneys and cancer. [ABSTRACT FROM AUTHOR]

Acute myeloblastic leukemia (AML) is a disease with a high rate of relapse and drug resistance due to the remaining leukemic stem cells (LSCs). Therefore, LSCs are specific targets for the treatment of leukemia. CD123 is specifically expressed on LSCs and performs as a specific marker. Curcumin is the main active compound of a natural product with low toxicity for humans. It has been reported to inhibit leukemic cell growth. However, curcumin is practically insoluble in water and has low bioavailability. In this study, we aimed to formulate curcumin nanoparticles and conjugate with the anti-CD123 to overcome the low water solubility and improve the targeting of LSCs. The cytotoxicity of both curcumin-loaded PLGA/poloxamer nanoparticles (Cur-NPs) and anti-CD123-curcumin-loaded PLGA/poloxamer nanoparticles (anti-CD123-Cur-NPs) were examined in KG-1a cells. The results showed that Cur-NPs and Cur-NPs-CD123 exhibited cytotoxic effects on KG-1a cells with the IC50 values of 74.20 ± 6.71 and 41.45 ± 5.49 µM, respectively. Moreover, anti-CD123-Cur-NPs induced higher apoptosis than Cur-NPs. The higher uptake of anti-CD123-Cur-NPs in KG-1a cells was confirmed by using flow cytometry. In conclusion, the anti-CD123-Cur-NPs formulation improved curcumin’s bioavailability and specific targeting of LSCs, suggesting that it is a promising drug delivery system for improving the therapeutic efficacy against AML.

Background:Alpha-synuclein is a member of synuclein family of proteins with unidentified function localized in the cytoplasm, mitochondria of neurons, and presynaptic nerve endings. Although it is found in the Lewy bodies in synucleinopathies and in Alzheimer’s disease, the protein could also be considered as a novel marker in diagnosis of diseases related to the hematopoietic system. Methods: The current study evaluated alpha-synuclein expression in bone marrow sections obtained from 9 patients with acute myeloblastic leukemia (AML)-M6, 2 patients with AML-M7, and 56 patients with other forms of AML by immunohistochemical (IHC) analysis Results: Seven out of 9 cases with erythroleukemia (66.7%) and 1 of the 2 cases with M7 (50%) were positive. In contrast; the blasts in 2 out of 56 AML cases with non-M6/M7 (3.6%) showed positive staining. Accordingly, alpha-synuclein was positive in normal erythroid precursors and megakaryocytes (if existing) in these cases; while, it was negative in lymphoid and myeloid precursors. Conclusion: Alpha-synuclein expression in non-neoplastic and neoplastic erythroid cells and megakaryocytes could be used as a complementary and useful marker for distinction between AML-M6/M7 and other types of AML

One of the diagnostic criteria for Acute Myeloblastic Leukemia (AML) is the presence of 20% myeloid blasts in peripheral blood or bone marrow. Some cases with recurrent cytogenetic abnormalities also fall in this category with blast cell count less than 20%. Thus, in the presence of these genetic abnormalities, the patients are classified as AML regardless of blast cell count. One of these genetic heterogeneities is t(8; 21) (q22, q22.1) which is more commonly seen in children and young adults. In this study, a 14-year-old boy is reported with a final diagnosis of AML, which was presented with fever and bicytopenia, clinically suspicious for acute leukemia. Laboratory results reported less than 20% blasts in bone marrow aspiration smears but genetic alteration t(8; 21) (q22, q22.1) was detected by molecular exams.

Background/aim: To analyze the long-term outcome of pediatric patients with acute myeloblastic leukemia., Materials and Methods: Data from 69 patients 0-18 years of age diagnosed between December 2001 and October 2019 were analyzed in April 2023. Patients received MRC-AML10 chemotherapy (2ADE+MACE+MidAC). No maintenance chemotherapy or preventive cranial radiotherapy was administered. Twelve patients with Down syndrome and 15 patients with promyelocytic leukemia were in the cohort. Patients with Down syndrome received reduced chemotherapy (cumulative anthracycline 420 mg/m 2 , cytarabine 3.4 g/m 2 , etoposide 1400 mg/m 2 ). ATRA was added to chemotherapy in promyelocytic leukemia., Results: Four patients (5.8%) died in the induction (two typhlitis, one intracranial hemorrhage, and one resistant disease). The complete remission rate of 66 patients was 87.8%. There was one death due to cardiotoxicity. Total infection-related deaths were 7.2%. Seven patients with high-risk criteria and one with resistant disease underwent hematopoietic stem cell transplantation (HSCT) following the first-line treatment. All seven patients in remission were alive and disease-free. The relapse rate was 34.4% (n = 21). Four patients developing marrow relapse were disease-free in the second remission after salvage and maintenance chemotherapy. Thirteen patients (18.84%) underwent HSCT in the second remission and 8 are alive and disease-free. The mean follow-up period of patients from diagnosis was 185 ± 13 months. Thirty-four patients (49.2%) were alive and disease-free in the first remission whereas another two patients in the first remission developed secondary malignancy. In good, standard, and poor risk groups, event-free survival (EFS) rates were 68.2%, 52.9%, and 10%, and overall survival (OS) rates were 86.4%, 79.4%, and 20%, respectively. Fifteen years of EFS and OS of the whole cohort were 49.3% and 69.6%, respectively., Conclusion: When compared with national data and multicenter studies of developed countries, survival rates were acceptable., Competing Interests: Conflict of interest: There is no conflict of interest of any author that may have influenced the presentation of the research., (© TÜBİTAK.)

A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson’s disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13×20×19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient’s condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died. [ABSTRACT FROM AUTHOR]

Objective: Natural killers (NK) cell function is mainly controlled by the expression of killer immunoglobulin-like receptors (KIRs) and their ligation with the corresponding ligands. The objective of this study was to investigate the putative association of KIRs, HLA class I ligands, and KIR/ligand combinations with rates of development of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Materials and Methods: The KIR/HLA I genotypes of 82 patients with leukemia (ALL, n=52; AML, n=17; and CML, n=13) were determined by PCR-SSP method and compared with genotypes of healthy controls (n=126). Results: KIR genotype frequency differed significantly between myelogenous leukemia patients and healthy controls for KIR2DL5A (17.6% vs. 47.7%, p=0.02), KIR3DS1 (17.6% vs. 47.6%, p=0.02), and KIR2DS4*001 (36.6% vs. 20.2%, p=0.017). The incidence of homozygous HLA-BBw4 (31.0% vs. 12.5%, p=0.042) and HLABw4Thr80 Thr80 (13.0% vs. 1.2%, p=0.01) was significantly elevated in myeloid leukemia patients compared to healthy controls. KIR/HLA class I ligand profile KIR3DS1(+)/L (-) was decreased and KIR3DL2(+)/ HLA-A3/11(-) was increased among myeloid leukemia cases compared to controls. Conclusion: These data suggest that the activity of NK cells as determined by inherited KIR/HLA class I ligand polymorphisms influences the susceptibility to myelogenous leukemia, but not to lymphoblastic leukemia. Additionally, the KIR genotype characterized by the absence of the inhibitory KIR2DL2 and the activating KIR2DS2 and KIR2DS3 (ID2) was found at a lower frequency in patients compared to controls, which confirmed the need for complex analysis based on all possible KIR/HLA class I ligand polymorphism combinations. [ABSTRACT FROM AUTHOR]

To study the caregiver burden and its correlates among the caregivers of adolescent and adult subjects with acute myeloblastic leukemia (AML). 30 caregivers of patients with AML were evaluated on family burden interview schedule (FBI), Caregiver Strain Index, multi-dimensional aspect of perceived social support scale, Cognitive-Behavioural Avoidance Scale, ways of coping checklist and General Health Questionnaire. Caregivers of patients with AML reported high caregiver burden (FBI objective burden score: 27.8; subjective burden score: 1.43). Among the various domains of FBI, the mean scores were highest for the domain of disruption of family activities and this was closely followed by disruption of family leisure. Patients with lower family income reported higher subjective and objective burden and were more overwhelmed. Patients belonging to lower socioeconomic status reported more financial burden. Caregiver burden was higher among caregivers who reported lower perceived social support, who more often used avoidance and escape as coping and less often used acceptability–responsibility and positive appraisal coping. Higher caregiver burden is associated with higher psychological morbidity. Caregivers of subjects with AML experience high level of caregiver burden and it is associated with lower social support and more often use maladaptive coping strategies. [ABSTRACT FROM AUTHOR]

Introduction: The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems. The aim of this work is analyzing the miRNA expression profiles in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) and hematopoietic conditions induced by non-tumor pathologies (NTP). Methods: A total of 114 cytological samples obtained by sternal puncture and aspiration biopsy of bone marrow (22 ALLs, 44 AMLs, and 48 NTPs) were analyzed by real-time PCR regarding preselected 25 miRNAs. For the classification of the samples, logistic regression was used with balancing of comparison group weights. Results: Our results indicated potential feasibility of (i) differentiating ALL+AML from a nontumor hematopoietic pathology with 93% sensitivity and 92% specificity using miR-150:miR-21, miR-20a:miR-221, and miR-24:nf3 (where nf3 is a normalization factor calculated from threshold cycle values of miR-103a, miR-191, and miR-378); (ii) diagnosing ALL with 81% sensitivity and 81% specificity using miR-181b:miR-100, miR-223:miR-124, and miR-24:nf3; and (iii) diagnosing AML with 81% sensitivity and 84% specificity using miR-150:miR-221, miR-100:miR-24, and miR-181a:miR-191. Conclusion: The results presented herein allow the miRNA expression profile to de used for differentiation between AL and NTP, no matter what AL subtype.

ABSTRACT: BACKGROUND: Leukemia defined as the cancer of bone marrow i.e. leading to wild proliferation of blood forming cells. The WBCs are granulocytes, which avert bacterial infection and T and B lymphocytes. Prognostic measures for the disease are still not clear whereas, in children prognosis rate is better as compared to adults. MATERIALS AND METHODS: Fifty (n=50) patients of leukemia and fifty (n=50) were obtained and screened at Ganga Ram Hospital Lahore. Serum was separated and estimated for their 8hydroxy -2-deoxy guanosine, Isoprostanes, myeloperoxidase and cytokines such as TNF-α and several interleukins with their commercially available ELISA kits respectively. While neutrophils were estimated by the help of hematology analyzer and malondialdehyde (MDA) was estimatedby the method of Ohkawa. RESULTS: The results of the present study shows that variables of oxidative stressi.e., malondialdehyde (MDA), isoprostanes (IsoP-F2a), 8-hydroxy-2-deoxy guanosine (8-OHdG), neutrophils and cytokines including interleukin-6 (IL-6), tumor necrosis factor (TNF) and myeloperoxidase (MPO)differed significantly. The recorded levels of MDA (5.26±1.26 nmoles/ml), Isoprostanes (81.26±5.26 pg/ml), 8-OHdG (1.22±0.016 pg/ml), MPO (2.16±0.16 pg/ml) were significantly increased as compared to controls. Levels of cytokines i.e., IL-6 and TNF-α remained (6.59±2.16pg/ml) and (56.26±2.26 pg/ml) in diseased group while in controls they were(0.965±0.16pg/ml) and (0.15±0.015pg/ml)respectively. CONCLUSION: Performed research work concludes that leukemic patients have positive relation among disease progression and oxidative stress. It is characterized by increased the levels of oxidative stress markers significantly in serum concentration. Increased level of MDA signifies increased lipid peroxidation in the subjects of leukemic patients.

Experiences with new multikinase inhibitors are limited, especially in children. In this report we summarize our experience with 2 patients with relapsed acute myeloblastic leukemia (AML), one with FMS-like tyrosine kinase- 3-internal tandem duplication mutation and the other with a single base mutation (D835Y). Both patients received sorafenib, one for 19 days and the other for 42 days, with clofarabine-including chemotherapy. One additionally received sunitinib for a total of 20 days. Both patients developed severe pancytopenia, hypertension, life-threatening bleedings from the gastrointestinal system, and, finally, intrapulmonary hemorrhage. Although both reached severe aplasia of the bone marrow without blastic infiltration, death occurred with neutropenic sepsis.

In the last decade, advancements in understanding the genetic and molecular mechanisms of acute myeloid leukemia (AML) have significantly improved treatment options. Techniques such as immunophenotyping, cytogenetics, and next-generation sequence (NGS) testing are now standard practices for patient assessments, allowing for personalized therapies based on individual patient needs. Our study aimed to evaluate the impact of cytogenetics and NGS on initial treatment decisions for AML at our institution. We analyzed the frequency of alternative therapy choices that could have been made with complete molecular and cytogenetic information and compared overall survival rates between patient groups. We also analyzed the turnaround time for result generation. Our retrospective study evaluated 39 AML patients treated at our university hospital from June 2020 to June 2022, excluding classic acute promyelocytic leukemia cases. Patients with incomplete data or concurrent hematological malignancies were excluded. We collected data on admission blood counts, European LeukemiaNet (ELN) risk stratification, Charlson score, treatment type, and timing of cytogenetics and NGS results. Patients were categorized into 'standard' or 'other therapy' groups based on their molecular and cytogenetic profiles in accordance with NCCN guidelines. Our main goal was to determine how often NGS and cytogenetics results could have influenced induction therapy choices. Secondary objectives included comparing overall survival rates and analyzing report turnaround times for NGS and cytogenetics. Our study found that out of the 39 AML patients, 17 were in the "standard" group, and 22 were in the "other therapy" group. The standard group had an average age of 62.59 years, an average time to chemotherapy initiation of 8.29 days, and an overall survival (OS) rate of 428.12 days. The other therapy group had an average age of 61.86 years, an average time to chemotherapy initiation of six days, and an OS rate of 258.64 days. There was a significant difference in survival rates between the two groups (p=0.009). According to the ELN stratification, the standard group had 11 patients at intermediate risk and six at adverse risk. In contrast, the other therapy group had seven at intermediate risk, four at good risk, and 11 at adverse risk. NGS revealed mutations in 58.97% of patients. Our study suggests that almost half of the patients could have been treated differently if complete molecular and cytogenetic information had been available before therapy initiation, highlighting the potential for more personalized treatments. Additionally, our results showed significant differences in overall survival rates between standard treatment and alternative therapy groups. Our findings emphasize the importance of timely NGS and cytogenetics result generation, guiding institutions to allocate resources for effective patient care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Devarkonda et al.)

Acute myeloblastic leukemia (AML) is the most prevalent form of AML in adults. Despite the availability of various treatment options, including radiotherapy and chemotherapy, many patients fail to respond to treatment or relapse. Copper is a necessary cofactor for all organisms; however, it turns toxic when concentrations reach a certain threshold maintained by homeostatic systems that have been conserved through evolution. However, the mechanism through which excess copper triggers cell death remains unknown. In this study, data on long non-coding RNAs (lncRNAs) related to cuproptosis were retrieved from publicly available databases. LASSO and univariate and multivariate Cox regression analyses were performed to establish an lncRNA model associated with cuproptosis specific to AML. To investigate the risk model, the Kaplan-Meier curve, principal component analysis, functional enrichment analysis, and nomographs were employed. The underlying clinicopathological characteristics were determined, and drug sensitivity predictions against the model were identified. Six cuproptosis-related lncRNA-based risk models were identified as the independent prognostic factors. By regrouping patients using a model-based method, we were able to more accurately differentiate patients according to their responses to immunotherapy. In addition, prospective compounds targeting AML subtypes have been identified. Using qRT-PCR, we examined the expression levels of six cuproptosis-associated lncRNAs in 30 clinical specimens. The cuproptosis-associated lncRNA risk-scoring model developed herein has implications in monitoring AML prognosis and in the clinical prediction of the response to immunotherapy. Furthermore, we identified and verified the ceRNA of the cuproptosis-related lncRNA HAGLR/miR-326/CDKN2A regulatory axis using bioinformatic tools. HAGLR is highly expressed in AML and AML cell lines. HAGLR inhibition significantly reduced the proliferation of AML cells and promoted apoptosis. Elesclomol promotes the degradation of CDKN2A and inhibits the proliferation of AML cells. Elesclomol combined with si-HAGLR inhibited the AML progression of AML both in vitro and in vivo ., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Microvesicles (MV) have been identified as candidate biomarkers for treating acute myeloid leukemia (AML). This study investigated the effects of human umbilical cord-derived mesenchymal stem cell (hUCMSC)-derived MVs on apoptosis and autophagy in the KG-1 leukemic cell line., Methods: The hUCMSCs were cultured and characterized by flow cytometry. MVs were isolated by ultracentrifugation, and the concentration was determined using the Bradford method. The characteristics of MVs were confirmed using transmission electron microscopy, flow cytometry, and dynamic light scattering methods. KG-1 cells were treated with the desired concentrations of MVs for 24 h. The apoptosis induction and reactive oxygen species production were evaluated using flow cytometry. RT-PCR was performed to evaluate apoptosis- and autophagy-related genes expression., Results: Following tretment of KG-1 cells with 25, 50, and 100 μg/ml concentrations of MVs, the apoptosis rates were 47.85%, 47.15%, and 51.35% (p < 0.0001), and the autophagy-induced ROS levels were 73.9% (p < 0.0002), 84.8% (p < 0.0001), and 85.4% (p < 0.0001), respectively. BAX and ATG7 gene expression increased significantly at all concentrations compared to the control, and this level was higher at 50 μg/ml than that of the other concentrations. In addition, LC3 and Beclin 1 expression increased significantly in a concentration-dependen manner. Conversely, BCL2 expression decreased compared to the control., Conclusion: Our findings indicate that hUCMSC-MVs could induce cell death pathways of autophagy and apoptosis in the KG-1 cell lines and exert potent antiproliferative and proapoptotic effects on KG-1 cells in vitro. Therefore, hUCMSC-MVs may be a potential approach for cancer therapy as a novel cell-to-cell communication strategy.

BACKGROUND: Leukemia defined as the cancer of bone marrow i.e. leading to wild proliferation of blood forming cells. The WBCs are granulocytes, which avert bacterial infection and T and B lymphocytes. Prognostic measures for the disease are still not clear whereas, in children prognosis rate is better as compared to adults. MATERIALS AND METHODS: Fifty (n=50) patients of leukemia and fifty (n=50) were obtained and screened at Ganga Ram Hospital Lahore. Serum was separated and estimated for their 8-hydroxy-2-deoxy guanosine, Isoprostanes, myeloperoxidase and cytokines such as TNF-a and several interleukins with their commercially available ELISA kits respectively. While neutrophils were estimated by the help of hematology analyzer and malondialdehyde (MDA) was estimatedby the method of Ohkawa. RESULTS: The results of the present study shows that variables of oxidative stressi.e., malondialdehyde (MDA), isoprostanes (IsoP-F2a), 8-hydroxy-2-deoxy guanosine (8-OHdG), neutrophils and cytokines including interleukin-6 (IL-6), tumor necrosis factor (TNF) and myeloperoxidase (MPO)differed significantly. The recorded levels of MDA (5.26±1.26 nmoles/ml), Isoprostanes (81.26±5.26 pg/ml), 8-OHdG (1.22±0.016 pg/ml), MPO (2.16±0.16 pg/ml) were significantly increased as compared to controls. Levels of cytokines i.e., IL-6 and TNF-a remained (6.59±2.16pg/ml) and (56.26±2.26 pg/ml) in diseased group while in controls they were(0.965±0.16pg/ml) and (0.15±0.015pg/ml)respectively. CONCLUSION: Performed research work concludes that leukemic patients have positive relation among disease progression and oxidative stress. It is characterized by increased the levels of oxidative stress markers significantly in serum concentration. Increased level of MDA signifies increased lipid peroxidation in the subjects of leukemic patients. [ABSTRACT FROM AUTHOR]

Risk factors of CMV replication in early period after allo-HSCT (D0‑D100) were – myeloablative conditioning – HR 3.74 (1.67–8.37), р = 0.001; unrelated donor – HR 2.18 (0.86–5.26), р = 0.10; HLA-matched donor – HR 0.24 (0.05–1.06), р = 0,06. In late posttransplant period (from D+100) significant risk factors of CMV-reactivation were (according to multivariate analysis) myeloablative conditioning – HR 13.17 (3.00–57.86), р = 0.001; combination of pretransplant remission of leukemia and using cyclosporine and methotrexate – HR 0.13 (0.03–0.50), р = 0.003; combination of aGVHD and CMV reactivation in early posttransplant period – HR 2.71 (0.86–8.50), р = 0.088; using of bone marrow – HR 0.37 (0.12–1.19), р = 0.095. We revealed the significant association of aGVHD and CMV-reactivation –OR 2.91 (1.07–7.92), р=0.006, and increased rate of cGVHD in patients with CMV replication at third month after allo-HSCT OR – 2.29 (1.03–5.08), р = 0.066. We revealed a tend to decreasing relapse risk in patients who had CMV-replication – HR 0.07 (0.004–1.17), р = 0.06. Cumulative incidence of CMV-disease was 28 %. CMV-disease was lethal in 44 % patients.