Evolving insights on histone methylome regulation in human acute myeloid leukemia pathogenesis and targeted therapy

AML is characterized by uncontrolled proliferation of clonal hematopoietic precursor cells. This interrupts normal hematopoiesis and may lead to bone marrow failure. It predominantly occurs in older adults, with the average age at diagnosis being 68 years (1). Intensive chemotherapy combined with hematopoietic stem cell (HSC) transplantation has considerably improved outcomes in younger adults. However about 80% of older adults still succumb to the disease or to the associated therapeutic toxicity (2).
Source: Experimental Hematology - Category: Hematology Authors: Tags: Review Source Type: research

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Patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) relapsed or refractory (R/R) acute myeloid leukemia (AML) have a dismal prognosis and limited effective treatment options outside of clinical trials [1-3]. In patients with R/R AML, performing a hematopoietic stem cell transplant (HSCT) after first salvage therapy decreases the risk of relapse and improves relapse-free survival (RFS) and overall survival (OS) probabilities [4]. Traditional cytotoxic salvage chemotherapy has been largely ineffective in controlling FLT3-ITD R/R disease, enabling ≤ 20% of patients to proceed to HSCT [5,6].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
AbstractPrior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R A...
Source: Annals of Hematology - Category: Hematology Source Type: research
Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations. AbstractTo explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next ‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction che...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Publication date: Available online 18 September 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Yu-juan Xue, Yi-fei Cheng, Ai-dong Lu, Yu Wang, Ying-xi Zuo, Chen-hua Yan, Pan Suo, Le-ping Zhang, Xiao-jun Huang
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Discussion: The present study evaluated the potential prognostic role of WBC count nadir and duration of aplasia, demonstrating that they are not associated with treatment outcomes in adult patients with AML treated with intensive chemotherapy. Therefore, a short duration of aplasia seems not linked to poor therapeutic efficacy in clearing bone marrow blasts. Our findings, although needing validation in larger and more homogeneous cohorts, may offer helpful clues in the management of aplasia of AML patients.Chemotherapy
Source: Chemotherapy - Category: Cancer & Oncology Source Type: research
Conclusions: The case expands the understanding of secondary CML and emphasizes the importance of oncological vigilance in patients with secondary CML after AML therapy. PMID: 32936052 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
The treatment option for children with intermediate-risk acute myeloid leukemia (IR-AML) in first complete remission is controversial. We retrospectively analyzed the outcomes of 80 children with IR-AML, and compared the effect of chemotherapy with haplo-HSCT as post-remission treatment. Compared with chemotherapy group, haplo-HSCT group had a significantly lower risk of relapse, especially in patients with minimal residual disease ≥10-3 after induction therapy.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and treatment-related acute myeloid leukemia (tAML) after chemotherapy or radiation therapy for other neoplasms are associated with poor outcomes. CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, has been shown to improve outcomes in AML-MRC and tAML compared with standard 7+3 regimens. Here we report the cases of four consecutive patients with AML-MRC or tAML who received CPX-351 as outpatient induction therapy immediately followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two patients received allo-HS...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: As the role and efficacy of autologous HDCT/ABSCT are not established in the analyzed entities, the indication for PBSC collection should be reanalyzed in regular intervals. Moreover, PBSC grafts from patients who have deceased, have insufficient grafts, or have already undergone an allogeneic TPL should be considered for disposal or (if applicable) for research use, to economize storage costs on a rational basis.Transfus Med Hemother
Source: Transfusion Medicine and Hemotherapy - Category: Hematology Source Type: research
Contributors : Sarah Ebinger ; Binje Vick ; Johannes Bagnoli ; Tobias Herold ; Irmela JeremiasSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensResistance against chemotherapy remains a major obstacle in treating patients with acute myeloid leukemia (AML). Novel therapeutic concepts are especially desired to target and eliminate resistant AML stem cells. Here we show that AML stem cells harbor the plasticity to switch from a low-cycling, therapy resistant state into an actively proliferating state associated with treatment response. We used patient-derived xenograft (PDX) cells from pa...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
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