Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification

Kansal, Rina

doi:10.20892/j.issn.2095-3941.2016.0001

Cited by 24 publications

(23 citation statements)

References 68 publications

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“…These abnormalities lead to the accumulation apjcb.waocp.com Oum kaltoum Ait Boujmia, et al: Characteristics and Survival of 927 Moroccan Adults with Acute Myeloid Leukemia cells [13] and the new classification WHO is based on the immunophenotypic, genetic and cytogenetic characteristics [14]. Cytogenetic abnormalities are described in the most of AML types and implicated in the diagnosis; prognosis and therapeutic response that make karyotype an indispensable examination in evaluating this cancer [15][16][17][18]. Immunophenotyping is an essential complement to cytogenetic analysis; it allows to refine the diagnosis of AML or even to modify it [19].…”

Section: Introductionmentioning

confidence: 99%

Characteristics and Survival of 927 Moroccan Adults with Acute Myeloid Leukemia: Monocentric Experience

Boujmia

Lamchahab

Hda

et al. 2021

Asian Pac J Cancer Biol

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Acute myeloïd leukemia (AML) is the most frequent form of acute leukemia among adults and the most aggressive type of leukemia, which is associated with the lowest survival rate. Patients with AML are treated with intensive chemotherapy and many factors could influence the survival of these patients, such as age, cytogenetic abnormalities; white blood cell (WBC) counts. The aim of this work was to study the epidemiological and response profiles of AML adults patients in Morocco.Patients and Methods: A prospective, descriptive study conducted in the Hematology and Pediatric Oncology department, 20 August Hospital Casablanca, and concerned adult patients diagnosed with AML through a period of seven years (January 2011 to December 2017). Statistical analysis was performed using SPSS version 20. The overall survival and disease-free survival were evaluated by using the Kaplan–Meier method. Results: A total of 927 patients diagnosed with AML during the 7 year period. 466 (50.3%) were males and 461 (49.7%) were females. The median age of patients was 46years.The most represented age group was between 18 and 60 years old with a percentage of 83.2%.The FAB subtype M2 occurred most frequently (27%) followed by M1 (24.8%). The cytogenetic study showed that the majority of patients had a normal karyotype. The t (8; 21) was the most detected balanced translocation in our series and the intermediate cytogenetic group was the most represented group (65.4%). A total of 461 patients (53.54%) were treated according to the protocol AML11. The Disease-free survival (DFS) was significantly better for favorable cytogenetic group as compared to other cytogenetic groups (median survival of 41.58 months for the favorable group versus 29.07 months for the adverse group; p-value = 0.02).Conclusion: The age of AML patients was younger compared to other populations. The majority of patients had a normal karyotype and the commonest balanced translocation was the t (8; 21). Survival was higher in patients with good prognosis.

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Section: Introductionmentioning

confidence: 99%

Characteristics and Survival of 927 Moroccan Adults with Acute Myeloid Leukemia: Monocentric Experience

Boujmia

Lamchahab

Hda

et al. 2021

Asian Pac J Cancer Biol

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“…1,2 In an era of precision medicine, the use of molecular genetic data, in particular, has fundamentally shaped the diagnostic approach to patients with AML. 3 Genetic profiling has led to more accurate diagnostic classification and improved risk stratification and identification of potential therapeutic targets. 1 Acute myeloid leukaemia is a genetically heterogeneous disease.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation of NPM1 and FLT3-ITD mutations in a central South African adult de novo acute myeloid leukaemia cohort

Kloppers

Kock

Cronje

et al. 2021

African Journal of Laboratory Medicine

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Background: Recognition of molecular abnormalities in acute myeloid leukaemia (AML) has improved our understanding of its biology. NPM1 and FLT3-ITD mutations are recurrent in AML and clinically significant. NPM1 mutations are associated with a favourable prognosis, while FLT3-ITD mutations are an independent poor prognostic factor in AML.Objective: This study described the prevalence and molecular characteristics of the NPM1 and FLT3-ITD mutations in a newly diagnosed AML patient cohort in central South Africa.Methods: The study included 40 de novo AML patients. An NPM1 and FLT3-ITD multiplex polymerase chain reaction assay was optimised to screen patients for the respective mutations and were confirmed using Sanger sequencing. The prevalence of the NPM1 and FLT3-ITD mutations were determined, and mutation-specific characteristics were described in relation to patients’ demographic information and AML classifications.Results: The patients’ median age was 38.5 years, with 77.5% (n = 31) of patients being self-proclaimed Black Africans. AML with recurrent genetic abnormalities was most prevalent (57.5%; n = 23), of which acute promyelocytic leukaemia (APL) was most common (40.0%; n = 16). None of the patients had the NPM1 mutation. FLT3-ITD was present in 37.5% (6/16) of APL patients and in one (20.0%) of five AML patients with a t(8;21) translocation. Most patients had an FLT3-ITD allele ratio of ≥ 50% and ITD lengths of 39 bp.Conclusion: FLT3-ITD mutations were mainly found in APL cases at a similar prevalence as reported in the literature. High FLT3-ITD allele ratios and long ITD lengths predominated. No NPM1 mutations were detected.

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“…Acute myeloid leukemia (AML) is a complex malignancy with significantly genetic mutation and deleterious epigenetic differentiation characterized by the clonal expansion of immature myeloid precursors. [1][2][3] The 5-year survival rates for AML are 5-15% in patients aged 60 years and older, as well as 35-40% for younger patients. 4,5 Until now, the main treatment for AML is allogenic hematopoietic cell transplantation and chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines.…”

Section: Introductionmentioning

confidence: 99%

<p>Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo</p>

Wu¹,

Cheng²,

Huang³

et al. 2020

DDDT

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Acute myeloid leukemia (AML) is a complex malignancy characterized by the clonal expansion of immature myeloid precursors. The standard treatment for newly diagnosed AML is chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines with disappointing clinical outcomes and severe adverse effects, such as symptomatic bradycardia, neurotoxicity. Thus, it is promising to treat AML through combination drug therapy to reduce the adverse effects of chemotherapeutics. In our recent published PNAS paper, we reported that NK-1R antagonists, both Aprepitant and SR140333, induce apoptosis of myeloid leukemia cells by inducing oxidative stress through mitochondrial calcium overload. We, therefore, tested the hypothesis of the combination Ara-C with NK-1R antagonist could enhance the efficacy of Ara-C. Methods: MTT assay was employed to detect the cell proliferation. Flow cytometry was applied to detect the cell cycle and necrosis. PI uptake and LDH release assay were used to detect the disintegration of the plasma membrane. Xenograft model was constructed to explore the effect of combination Ara-C with Aprepitant in vivo. Results: Our results showed that Aprepitant sensitizes HL60 cells to the cytotoxic effects of Ara-C more than 5-fold by enhancing G0/G1 cell cycle arrest and necrosis in vitro. Furthermore, Nec-1, a specific inhibitor of necroptosis, could recover the cell proliferative viability significantly. Attractively, once every 2-days regimen of Ara-C (5 mg/kg) and Aprepitant (10 mg/kg) via in situ injection dramatically reduced the tumor volume from 2175.0 ± 341.9 mm 3 in the vehicle group to 828.4 ± 232.4 mm 3 in the combination group without obvious toxicity in human myeloid leukemia xenograft mice. Conclusion: Taken together, reduced dose of Ara-C combination with moderate Aprepitant provides more effective therapeutical methods for AML treatment in vitro and in vivo with the elimination of the toxicity of Ara-C, which may pay new avenue for the usage of the routine chemotherapy drug Ara-C with low dose to enhance efficacy and reduce toxicity in clinical practice.

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Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification

Cited by 24 publications

References 68 publications

Characteristics and Survival of 927 Moroccan Adults with Acute Myeloid Leukemia: Monocentric Experience

Characteristics and Survival of 927 Moroccan Adults with Acute Myeloid Leukemia: Monocentric Experience

Molecular characterisation of NPM1 and FLT3-ITD mutations in a central South African adult de novo acute myeloid leukaemia cohort

<p>Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo</p>

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