Core‐binding factor acute myeloid leukemia: Heterogeneity, monitoring, and therapy

Solh, Melhem; Yohe, Sophia; Weisdorf, Daniel J.; Üstün, Celalettin

doi:10.1002/ajh.23821

Cited by 59 publications

(95 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 51%

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Section: Characteristiccontrasting

confidence: 51%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…CBF AMLs generally represent an AML subgroup with a favorable outcome. 24 Comparing the expression levels of both mature miRNAs strands confirmed miR-139-5p to be the guide and miR-139-3p to be the passenger strand (Supplementary Figure 1b). The expression data suggested that miR-139-5p is upregulated in terminally differentiated myelomonocytic cells to control proliferation, whereas it is suppressed in normal and malignant stem and progenitor cells.…”

Section: Resultsmentioning

confidence: 68%

miR-139-5p controls translation in myeloid leukemia through EIF4G2

et al. 2015

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are crucial components of homeostatic and developmental gene regulation. In turn, dysregulation of miRNA expression is a common feature of different types of cancer, which can be harnessed therapeutically. Here we identify miR-139-5p suppression across several cytogenetically defined acute myeloid leukemia (AML) subgroups. The promoter of mir-139 was transcriptionally silenced and could be reactivated by histone deacetylase inhibitors in a dose-dependent manner. Restoration of mir-139 expression in cell lines representing the major AML subgroups (t[8;21], inv[16], mixed lineage leukemia-rearranged and complex karyotype AML) caused cell cycle arrest and apoptosis in vitro and in xenograft mouse models in vivo. During normal hematopoiesis, mir-139 is exclusively expressed in terminally differentiated neutrophils and macrophages. Ectopic expression of mir-139 repressed proliferation of normal CD34(+)-hematopoietic stem and progenitor cells and perturbed myelomonocytic in vitro differentiation. Mechanistically, mir-139 exerts its effects by repressing the translation initiation factor EIF4G2, thereby reducing overall protein synthesis while specifically inducing the translation of cell cycle inhibitor p27(Kip1). Knockdown of EIF4G2 recapitulated the effects of mir-139, whereas restoring EIF4G2 expression rescued the mir-139 phenotype. Moreover, elevated miR-139-5p expression is associated with a favorable outcome in a cohort of 165 pediatric patients with AML. Thus, mir-139 acts as a global tumor suppressor-miR in AML by controlling protein translation. As AML cells are dependent on high protein synthesis rates controlling the expression of mir-139 constitutes a novel path for the treatment of AML.

show abstract

“…Another study with 481 AML patients indicated that 20% of the CBF-AML cytogenetic group had FLT3 mutations 27 . On the other hand, KIT mutations have been observed for 6.6–46.1% of CBF-AML patients 28 . NPM1 plays an important role in ribosomal protein assembly, transport, prevents aggregation of nuclear proteins and regulates transcriptional activity of p53 26 .…”

Section: Cooperating Mutations In Cbf Leukemiamentioning

confidence: 99%

“…Although the CBF genetic rearrangements in AML patients are reported to be associated with relatively favorable prognosis 32,33 , only 40–60% of adult CBF-AML patients exhibit long-term survival 28 . Additionally all treatment regimens are associated with significant relapse related morbidity and mortality 34,35 .…”

Section: Prognosismentioning

confidence: 99%

“…Presence of co-operative NPM1 mutation provides favorable overall survival (OS) after intensive double-induction and consolidation therapy only in the absence of FLT3 26 whereas c-KIT mutations have the worst outcome in CBF-AML patients with 56% relapse rate 28,40 . Though cooperating KIT mutation have not shown any significant effect on OS in inv(16), poorer OS has been observed for patients with t(8;21) 41,42 .…”

Section: Prognosismentioning

confidence: 99%

See 1 more Smart Citation

Core Binding Factor Acute Myeloid Leukemia: New Prognostic Categories and Therapeutic Opportunities

Sinha

Cunningham

Liu

2015

Seminars in Hematology

View full text Add to dashboard Cite

Core binding factor (CBF) is a heterodimeric protein complex involved in the transcriptional regulation of normal hematopoiesis. Mutations in CBF-encoding genes result in leukemogenic proliferative advantages and impaired differentiation of the hematopoietic progenitors. CBF molecular aberrations are responsible for approximately 20% of all adult acute myeloid leukemia (AML). Although CBF-AMLs are considered to have relatively good prognosis compared to other leukemia subtypes, they are a heterogeneous group of disorders and modern therapy frequently leads to relapse and the associated morbidity and mortality. Improvements in risk stratification and development of targeted therapies are needed for better outcomes. In this review we provide a brief overview of the molecular basis, prognostic categories and the advanced treatment strategies for CBF leukemias.

show abstract

Core‐binding factor acute myeloid leukemia: Heterogeneity, monitoring, and therapy

Cited by 59 publications

References 154 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

miR-139-5p controls translation in myeloid leukemia through EIF4G2

Core Binding Factor Acute Myeloid Leukemia: New Prognostic Categories and Therapeutic Opportunities

Contact Info

Product

Resources

About