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Introduction: Acute myeloid leukemia (AML) is a clonal cancer that develops from myeloid progenitors. P-glycoprotein (Pgp) is the membrane transporter encoded by the multidrug resistance (MDR1) gene, which is responsible for the efflux of several chemotherapeutic drugs for the treatment of AML. Pgp’s physiological role in normal cells is unknown. This contrasts with the lack of clarity on Pgp’s activity as an efflux pump in neoplastic or cancer cells. The association between Pgp and CD34 expression in adult patients with de novo AML was investigated in this study. Methods: Thirty participants were enrolled between November 2022 and April 2023. Immunophenotyping, Pgp percentage, and CD34 expression examinations using bone marrow aspirate blood were performed using immunoflowcytometry. The analysis of the correlation test was performed by Spearman correlation. Results: Patients with de novo AML had a median age of 42.5 years. The bone marrow aspiration results of adult patients with AML reveal the following distribution according to the French–American–British classification: 30% of patients have AML M1, 30% have AML M2, 13.33% have AML M3, 3.33% have AML M4, 16.66% have AML M5, and 6.66% have AML M7. There was no statistical correlation between Pgp and CD34 (P = 0.063), neither Pgp and leukocyte count (P = 0.442). Conclusions: Although no correlation between Pgp with CD34 or leukocyte count, it is necessary to consider the role of other members of the ABC transporter superfamily to further examine its relationship with CD34.

The authors present the case of a 39-year-old male with an initial diagnosis of de novo acute myeloid leukemia who, despite complete remission without measurable residual disease after conventional induction chemotherapy, presented with persistent splenomegaly and eosinophilia. As reactive eosinophilia was excluded and CBFB::MYH11 and RUNX1::RUNX1T1 gene fusions were not identified in additional molecular studies, we decided to test for other causes of clonal eosinophilia. Cytogenetic and molecular testing identified FIP1L1::PDGFRA gene fusion and prompted the introduction of imatinib. The initial diagnosis of de novo acute myeloid leukemia was changed to myeloid/lymphoid neoplasm with eosinophilia and FIP1L1::PDGFRA in the blast phase as myeloid blast count in the bone marrow at the diagnosis was >20%. The patient has maintained a complete molecular response with imatinib at a dose of 100 mg for more than two years. [ABSTRACT FROM AUTHOR]

Introduction: Acute myeloid leukemia (AML) is a clonal cancer that develops from myeloid progenitors. P-glycoprotein (Pgp) is the membrane transporter encoded by the multidrug resistance (MDR1) gene, which is responsible for the efflux of several chemotherapeutic drugs for the treatment of AML. Pgp's physiological role in normal cells is unknown. This contrasts with the lack of clarity on Pgp's activity as an efflux pump in neoplastic or cancer cells. The association between Pgp and CD34 expression in adult patients with de novo AML was investigated in this study. Methods: Thirty participants were enrolled between November 2022 and April 2023. Immunophenotyping, Pgp percentage, and CD34 expression examinations using bone marrow aspirate blood were performed using immunoflowcytometry. The analysis of the correlation test was performed by Spearman correlation. Results: Patients with de novo AML had a median age of 42.5 years. The bone marrow aspiration results of adult patients with AML reveal the following distribution according to the French–American–British classification: 30% of patients have AML M1, 30% have AML M2, 13.33% have AML M3, 3.33% have AML M4, 16.66% have AML M5, and 6.66% have AML M7. There was no statistical correlation between Pgp and CD34 (P = 0.063), neither Pgp and leukocyte count (P = 0.442). Conclusions: Although no correlation between Pgp with CD34 or leukocyte count, it is necessary to consider the role of other members of the ABC transporter superfamily to further examine its relationship with CD34. [ABSTRACT FROM AUTHOR]

Abstract We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p

We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are characterized by risk of relapses, poor survival, unwanted side effects and high toxicity with the current therapies. In light of these facts, there are efforts to develop new drugs specific for deregulated molecules that participate in leukemia pathogenesis. Hematopoietic cell kinase (HCK), an Src kinase family member, is overexpressed on hematopoietic stem cells of MDS and de novo AML patients and involved in the oncogenic process. Thus, we investigated in vitro, ex vivo and in vivo effects of a novel chemical compound targeting HCK inhibition (iHCK-37), in combination with the most used drugs for the treatment of MDS and de novo AML, 5-Azacytidine and Cytarabine. Herein, the combination treatment with iHCK-37 and 5-Azacytidine or Cytarabine demonstrated additive effects against leukemia cells, compared to either drug alone. iHCK-37 plus 5-Azacytidine or Cytarabine treatment was able to reduce the activation of oncogenic pathways, MAPK/ERK and PI3K/AKT, leading to reduction of ERK and AKT phosphorylation, and increased BAX and decreased BCL-XL protein expression. Moreover, treatment with iHCK-37 reduced MDS and AML CD34-positive cell numbers inside a 3D-structure but did not affect normal CD34-positive cell numbers. In vivo analysis showed that leukemic mice treated with iHCK-37 had reduced ERK and AKT proteins phosphorylation levels and leukocyte numbers. In conclusion, the iHCK-37 inhibitor has anti-neoplastic activity in leukemia cells without altering apoptosis and survival rate of normal cells, suggesting on-target malignant cell killing activity as a single agent or in combination with 5-Azacytidine or Cytarabine. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) accounts for approximately 25% of pediatric leukemia cases in Japan, with approximately 150 patients being newly diagnosed with AML annually. Pediatric acute myeloid leukemia is classified into three groups: myeloid leukemia associated with Down syndrome (ML-DS), acute promyelocytic leukemia (APL), and de novo AML. Patients with ML-DS have an event-free survival rate over 80%; however, relapsed patients have dismal outcomes, even if they receive hematopoietic cell transplantation. APL is curable with all-trans retinoic acid and arsenic trioxide. In de novo AML, 10% of patients fail to achieve remission, and approximately 30% of patients who successfully achieve remission subsequently experience AML relapse. This review highlights the therapeutic approach for these three diseases with context from past clinical studies in Japan, and shares promising new therapeutic options for relapsed/refractory de novo AML.

AIM: To study the specific features of de novo acute myeloid leukemia (AML) with FLT3-ITD mutation/MATERIAL AND METHODS: The results of examination were analyzed in 101 patients. Bone marrow morphological specimens were stained with Pappenheim stain. The karyotype was investigated using the standard GTG-banding method. Blast cells were immunotyped in a five-color analysis on a Cytomics FC 500 laser flow cytofluorometer/RESULTS: FLT3-ITD mutation was identified in 21 patients who had a varying morphological nature of blasts, different karyotype variants, and frequently additional NPM1 gene mutation. The distinctive property of 10 patients with normal karyotype and FLT3-ITD mutation (without NPM1 gene mutation) was the larger number of cases with high expression of HLA-DR and CD7 than in the control group that included 18 patients with normal karyotype AML without FLT3-ITD nutation: 50% versus 6.2% (p=0.007) and 100% versus 55.6% (p=0.014), respectively/CONCLUSION: Normal karyotype AML with FLT3-ITD mutation is a group that is homogeneous in the biological phenotype of leukemia cells.

Key Clinical Message Mixed phenotype acute leukemia with t(9;22) is a rare disease with poor prognosis, and information on optimal treatment is limited. We describe a case where our patient experienced positive outcome after nonacute myeloid leukemia-type intensive induction therapy followed by postremission therapy with stem cell transplant. [ABSTRACT FROM AUTHOR]

The t(11; 20)(p15;q11 ~ 12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11; 20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46, XY, t(2; 5) (q33;q31),t(11; 20)(p15;q12)[20]. Expression of the NUP98/ TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46, XY, t(2; 5) (q33;q31)[19]/46, sl, t(11; 20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2; 5) was centromeric to EGR1 . In all 10 cases described in the literature, the NUP98 exon 13/ TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11; 20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML. [ABSTRACT FROM AUTHOR]

High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-specific prognostic factors and to develop prognostic scores for both patient groups. A total of 692 patients in the EORTC/GIMEMA AML-10 study and 289 patients in the CRIANT study received identical remission-induction and consolidation treatment. Estimated 5-year survival rate was 34 % in the AML-10 versus 27 % in the CRIANT study, and estimated disease-free survival was 40 % versus 28 %, respectively. In multivariate analysis, cytogenetic characteristics, white blood count, and age appeared prognostic for survival in both studies. French-American-British (FAB) subtype and performance status were prognostic in the AML-10 study only, whereas number of cytopenias and duration of antecedent hematologic disorder >6 months were prognostic in the CRIANT study only. The prognostic scores distinguish three groups with a 5-year survival rate of 54, 38, and 19 % in the AML-10 study versus 69, 37, and 5 % in the CRIANT study. The prognostic value of these scores has been validated on two external series. The new scoring systems form a practical tool to predict the outcome of individual MDS and AML patients treated with intensive antileukemic therapy. [ABSTRACT FROM AUTHOR]

Background: Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) both result in dismal outcomes. This retrospective study aimed to determine whether these features are poor prognostic factors independent of older age and adverse cytogenetics, which are commonly associated with a poor prognosis., Methods: The characteristics and real-world outcomes of sAML and AML-MRC from the Thai AML registry database were investigated., Results: From a total of 992 newly diagnosed AML patients, 315 (31.8%) patients were classified into sAML or AML-MRC subtypes. Older age, low white blood cell (WBC) count, low bone marrow blast, and adverse cytogenetic risk were commonly present in sAML and AML-MRC compared to de novo AML. Complete remission after 7 + 3 induction therapy occurred in 42.3% of patients with sAML or AML-MRC and 62.4% of de novo AML (P < .001). The median overall survival (OS) of sAML, AML-MRC, and de novo AML were 6.9, 7.0, and 12.2 months, respectively (P < .001). The independent prognostic factors for inferior OS were older age, intermediate-risk or adverse-risk cytogenetics, WBC count > 100 × 10 9 /L, poor performance status, and a subgroup of AML-MRC with the morphologic criteria of multilineage dysplasia (AML-MRC-M). In addition, sAML, AML-MRC, and a WBC count > 100 × 10 9 /L were pre-treatment prognostic factors associated with poor relapse-free survival (P = .006, P = .017, and P < .001, respectively)., Conclusion: Both sAML and AML-MRC are independently associated with poor outcomes in Thai patients. Our study supports AML-MRC-M as an adverse prognostic factor for OS., (Copyright © 2022 Elsevier Inc. All rights reserved.)