Prognosis and monitoring of core-binding factor acute myeloid leukemia: current and emerging factors

Duployez, Nicolas; Willekens, Christophe; Marceau-Renaut, Alice; Boudry-Labis, Elise; Preudhomme, Claude

doi:10.1586/17474086.2014.976551

Cited by 30 publications

(21 citation statements)

References 136 publications

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“…Patients with t-AML are more prone to a poor prognosis and cytogenetic findings. Core binding factor abnormalities are associated with an improved outcome in patients with AML (39)(40)(41). However, in the present cohort, t (15,17) appeared to have a good effect on the outcome of disease, even in patients with t-AML (42)(43)(44)(45).…”

Section: Characteristiccontrasting

confidence: 63%

Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

et al. 2016

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Abstract. Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified. Data regarding the patient demographics, primary diagnosis and treatment, age at onset of therapy-related myeloid neoplasm, latency time of the neoplasm, cytogenetic characteristics, AML therapy and outcome were collected from medical records. A previous diagnosis with solid tumors was present in 28 patients, and 10 patients possessed a history of hematological conditions, all a lymphoproliferative disorder. Breast cancer was the most frequent solid tumor identified (39.5% of all solid tumors diagnosed). The mean latency time was 3 years. In the present study, t-AML patients were older (P<0.001) and more frequently carried cytogenetic abnormalities (P= 0.009) compared with de novo AML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (P<0.001). However, in younger patients (age, <50 years) there was no difference between the overall survival time of patients with t-AML and those with de novo AML (P= 0.983). Additionally, patients with promyelocytic leukemia possess a good prognosis, even when AML occurs as a secondary event (P= 0.98). To the best of our knowledge, the present study is the first to evaluate t-AML in Portugal and the results are consistent with the data published previously in other populations. The present study concludes that although t-AML demonstrates a poor prognosis, this is not observed among younger patients or promyelocytic leukemia patients.

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Section: Characteristiccontrasting

confidence: 63%

Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

et al. 2016

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“…However, the molecular genetic abnormalities potentially explaining differences between these 2 subtypes of AML have not been explored in detail. Although implication of TK pathways in CBF AML leukemogenesis has been widely studied, 15 only a few reports have identified cooperating mutations in CBF AML outside of TK pathway alterations. Although the "2-hit model" of leukemogenesis mentioned earlier is biologically relevant, it is impossible to ignore the multitude of genetic and epigenetic aberrations that have recently been described in human leukemia.…”

Section: Discussionmentioning

confidence: 99%

“…However, patients with t(8;21) or inv (16) AML differ with respect to several biological and clinical features. 15 Morphologically, patients with t(8;21) AML frequently present with the French-American-British morphological subtype M2 or AML with maturation, whereas patients with inv(16) more often are diagnosed with the French-AmericanBritish subtype M4Eo or acute myelomonocytic leukemia with abnormal marrow eosinophils. 16 Moreover, gene expression profiling of CBF AML segregate t(8;21) and inv(16) patients into distinct subgroups, 17 reflecting different pathways activated in each subtype of CBF AML.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive mutational profiling of core binding factor acute myeloid leukemia

Duployez

Marceau-Renaut

Boissel

et al. 2016

Blood

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196

186

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Key Points• Recurrent mutations in chromatin modifiers and cohesin were observed in t(8;21) AML, but not inv (16 . Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML.

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“…Very recently, several studies have identified that ASXL1 and ASXL2 mutations are enriched in a very specific subset of AML, AML with t(8;21) (Huether et al 2014; Duployez et al 2015b), which represent ~10% of all AML. ASXL family member mutations occur in ~30% of pediatric and adult t(8;21) AML patients (Figs.…”

Section: Discovery Of Mutations In Asxl Gene Family Members In Cancermentioning

confidence: 99%

The Role of Additional Sex Combs-Like Proteins in Cancer

Micol

Abdel‐Wahab

2016

Cold Spring Harb Perspect Med

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Additional sex combs-like (ASXL) proteins are mammalian homologs of Addition of sex combs (Asx), a protein that regulates the balance of trithorax and Polycomb function in Drosophila. All three ASXL family members (ASXL1, ASXL2, and ASXL3) are affected by somatic or de novo germline mutations in cancer or rare developmental syndromes, respectively. Although Asx is characterized as a catalytic partner for the deubiquitinase Calypso (or BAP1), there are domains of ASXL proteins that are distinct from Asx and the roles and redundancies of ASXL members are not yet well understood. Moreover, it is not yet fully clarified if commonly encountered ASXL1 mutations result in a loss of protein or stable expression of a truncated protein with dominant-negative or gain-of-function properties. This review summarizes our current knowledge of the biological and functional roles of ASXL members in development, cancer, and transcription.

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Prognosis and monitoring of core-binding factor acute myeloid leukemia: current and emerging factors

Cited by 30 publications

References 136 publications

Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

Comprehensive mutational profiling of core binding factor acute myeloid leukemia

The Role of Additional Sex Combs-Like Proteins in Cancer

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