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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 The occurrence of acute leukemia in patients with sickle cell anemia is uncommon. The Philadelphia chromosome is the hallmark of chronic myeloid leukemia. However, it may also be associated with acute lymphoblastic leukemia and acute myeloblastic leukemia. The common BCR-ABL1 transcripts seen in acute lymphoblastic leukemia are e1a2, e13a2, and e14a2, while other transcripts such as e1a3, e13a3, and e6a2 occur rarely. This report describes the presentation, management, and outcome of the occurrence of B-cell acute lymphoblastic leukemia with the rare e1a3 BCR-ABL1 transcript in a patient with sickle cell anemia. Case presentation A 19-year-old male Nigerian, a known sickle cell anemia patient was admitted on account of severe vaso-occlusive crisis. Examination revealed fever, palor, and jaundice. Full blood count showed anemia and leukocytosis. Peripheral blood and bone marrow smears revealed numerous large and small lymphoblasts in keeping with the L2 subtype of acute lymphoblastic leukemia based on the French–American–British classification. Further evaluation was in keeping with a diagnosis of BCR-ABL1-positive mature B-cell acute lymphoblastic leukemia associated with the rare e1a3 transcript. He was commenced simultaneously on induction chemotherapy and Imatinib while being prepared for allogeneic stem cell transplantation. However, he died six months after diagnosis from meningoencephalitis. Conclusion The occurrence of acute lymphoblastic leukemia with a rare BCR-ABL1 e1a3 transcript in association with sickle cell anemia is uncommon and associated with poor prognosis.

Leukemia cutis (LC) is the infiltration of neoplastic leukocytes into the skin, causing skin lesions. In children, it appears more frequently in patients with acute myeloblastic leukemia (AML), particularly in subtypes with a monocytic component.We studied a retrospective cohort including all AML cases from the Hospital Infantil de México Federico Gómez between January 2009 to December 2019 and described the clinical characteristics of those who presented LC and other mucocutaneous manifestations. The information was collected from clinical records and analyzed using SPSS software (version 17).We identified 54 AML cases: 53.7% were males, and 75.9% of the patients presented at least one dermatosis in the course of the disease. LC was clinically present in 14.8% of patients and was histologically confirmed in 9.2% of them; two congenital leukemia cases were identified. Among these patients, LC was more frequent in males. LC patients were younger than those without LC, the most frequent AML subtype was M2 (37.5%), and the most frequent clinical manifestations were plaques, chloromas, and gingival hyperplasia. None of the patients presented LC before AML diagnosis.Currently, only a few studies about LC on pediatric populations have been reported, and the existing ones have small sample sizes. We found clinical and epidemiological similarities with other populations in the studied sample.La leucemia cutis (LC) es la infiltración de leucocitos neoplásicos a la piel que provoca lesiones cutáneas. En la población infantil aparece con más frecuencia en pacientes con leucemia mieloblástica aguda (LMA), principalmente en los subtipos con componente monocítico.Se estudió una cohorte retrospectiva en el Hospital Infantil de México Federico Gómez entre enero de 2009 y diciembre de 2019 para conocer las características clínicas de los pacientes con LMA que cursaron con LC y otras manifestaciones mucocutáneas. La información se recabó de los expedientes clínicos y se analizó con el programa estadístico SPSS versión 17.Se identificaron 54 casos de LMA: el 53.7% en el sexo masculino y el 46.3% en el sexo femenino. El 75.9% de los pacientes presentaron alguna dermatosis durante el curso de su enfermedad. La LC se presentó clínicamente en el 14.8% de los pacientes y se confirmó histológicamente en el 9.2% de ellos; dos casos correspondieron a leucemia congénita. De estos pacientes, la LC fue más frecuente en el sexo masculino, los pacientes fueron más jóvenes que el grupo sin LC, el subtipo de LMA más frecuente fue el M2 (37.5%) y las principales manifestaciones clínicas fueron placas infiltradas, cloromas e hiperplasia gingival. Ninguno de los pacientes presentó LC antes del diagnóstico de LMA.Hasta ahora existen pocos estudios de LC en las diferentes variedades de leucemia en la población infantil, y los existentes cuentan con un tamaño de muestra pequeño. En este estudio se reportan estadísticas descriptivas y se encuentran similitudes clínico-epidemiológicas con otras poblaciones.

Introduction: Acute erythroid leukemia (AEL) is a rare type of acute myeloblastic leukemia. Acute erythroid leukemia is characterized by a predominant erythroid proliferation, there are 2 subtypes: erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia… Myelodysplastic syndromes (MDS) are a group of biologically and clinically heterogeneous clonal disorders characterized by ineffective hematopoiesis and peripheral cytopenia due to high apoptosis The purpose to presenting this case is how to differentiate an acute erythroleukemia (AEL) from myelodysplastic syndrome (MDS). Case report. A 74-year-old man came to emergency room after he falling down from the stairs and then was hospitalized with a two weeks history of severe weakness, anorexia, weight loss. He suffered of diabetes mellitus type II insulin dependent, and HTA. The physical examination showed cutaneous and conjunctival pallor, large ecchymosis in the low extremities and hepatosplenomegaly. CBC showed: pancytopenia and macrocytosis, neutrophils 60%, normoblasts 4:100 and reticulocyte count 3%. Conclusions: The diagnosis was Acute Erythroid Leukemia. The % of myeloblasts in bone marrow was > 20% of non-erythroid cells. Erythroleukemia characterizes from hepatomegaly this is found and in our case. Differential diagnosis is based mainly in bone marrow aspiration, immunophenotyping (flow cytometry).

Granulocytic sarcoma, chloroma, myeloblastoma, or here referred as myeloid sarcoma (MS), is a rare extramedullary tumor composed of immature myeloid cells called myeloblasts. MS is seen most commonly in patients with acute myeloid leukemia and less frequently in chronic myeloid leukemia, myelodysplastic syndrome. In rarer instances, MS has been shown to precede the development of myeloid tumors by acute myeloblastic leukemia (AML). In particular, isolated MS involving spine is extremely rare. We herein present a rare case of isolated spinal MS in non-leukemic patient. This is a previously relatively healthy 47-year-old man who presented with signs of lumbar spinal cord compression, initially reported as schwannoma on imaging, later diagnosed with spinal MS on pathology. Further workup did not reveal any evidence of bone marrow or other hematological involvement. The patient successfully treated by L4/L5 laminectomy and debulking with subsequent radiation resulting in substantial decrease in size of tumor with significant improvement in symptoms during follow up. This case not only describes a rare case of isolated MS of lumbar spine, but also highlights the potential treatment challenges of such a rare diagnosis. We review the available literature, discuss available treatment options, and highlight the need for further investigations along with increased clinician awareness.

Acquired immune deficiencies caused by different etiologies, promote invasive fungal infections. When this immunity begins to improve, it can induce an excessive inflammatory response defined as Immune Reconstitution Inflammatory Syndrome (IRIS). Hepatosplenic Candidiasis (HSC) can be considered a form of IRIS syndrome as it occurs following neutrophil recovery in patients treated for acute leukemia. Differentiating IRIS from a single fungal infection or treatment failure due to a similar clinical picture is a real diagnostic problem. Misdiagnosis and subsequently ineffective treatment with antifungal therapy instead of anti-inflammatory drugs, may lead fatal course of the disease. A deep and prolonged neutropenia developed after the first induction chemotherapy in our two and a half-year-old male patient who was followed up in our clinic with the diagnosis of Acute Myeloblastic Leukemia (AML). Our patient had fever, abdominal pain as well as his Gamma Glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP) levels increased during neutropenia recovery. He was diagnosed with hepatosplenic candidiasis, by observing ‘target like abscesses’ on dynamic Magnetic Resonance Imaging (MRI) taken for his newly developing symptoms and laboratory findings while recovering neutropenia. After his first and third induction chemotherapy courses, his fever persisted although antifungal therapy, steroid treatment was initiated considering IRIS. After his re-intensification course, because of the same flare-up symptoms, we started immunglobulin in addition to steroid. With methylprednisolone and intravenous immunoglobulin, his symptoms improved and significant regression was observed in the lesions ‘target-like abscesses’ on MRI and in the laboratory values. Result: IRIS should be considered for patients with hepatic candidiasis whose have persistent fever despite appropriate antifungal therapy. Glucocorticoid should be started first for an anti-inflammatory effect.

Simple Summary The BCL2 family comprises pro- and anti-apoptotic proteins whose cellular abundance, modifications, and interactions determine the cell fate. Its contribution to pathogenesis of acute myeloid leukemia (AML) was not widely studied and none of the studies published before presented a complex picture of BCL2 family gene expression. Therefore, we decided to analyze the AML transcriptome sequencing data to outline this picture and look for relations between the expression of particular BCL2 family members and the genes encoding interacting proteins, presence of mutations, and clinical features. Our findings should not only shed light on apoptosis- and oncogenesis-related processes, but may also be implemented in clinical practice. Prognostic significance, association with response to therapy and potential application in the selection of therapeutic targets are of particular importance. Abstract The expression of apoptosis-related BCL2 family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of BCL2 family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in BMF, BNIP1, and HRK was statistically significant. In a group of patients resistant to chemotherapy, overexpression of BCL2L1 was manifested. In agreement with the literature data, our results reveal that BCL2L1 is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that BCL2 family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some BCL2 family members, in particular BIK and BCL2L13, were associated with poor outcome.