Advances in molecular genetics and treatment of core-binding factor acute myeloid leukemia

Abstract

Purpose of review Core-binding factor (CBF) acute myeloid leukemia (AML) is among the most common cytogenetic subtypes of AML, being detected in approximately 13% of adults with primary disease. Although CBF-AML is associated with a relatively favorable prognosis, only one-half of the patients are cured. Herein we review recent discoveries of genetic and epigenetic alterations in CBF-AML that may represent novel prognostic markers and therapeutic targets and lead to improvement of the still disappointing clinical outcome of these patients. Recent findings Several acquired gene mutations and gene-expression and microRNA-expression changes that occur in addition to t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), the cytogenetic hallmarks of CBF-AML, have been recently reported. Alterations that may represent cooperative events in CBF-AML leukemogenesis include mutations in the KIT, FLT3, JAK2 and RAS genes, haploinsufficiency of the putative tumor suppressor genes TLE1 and TLE4 in t(8;21)-positive patients with del(9q), MN1 overexpression in inv(16) patients, and epigenetic and posttranscriptional silencing of CEBPA. Genome-wide gene-expression and microRNA-expression profiling identifying subgroups of CBF-AML patients with distinct molecular signatures, different clinical outcomes, or both, have also been reported. Summary Progress has been made in delineating the genetic basis of CBF-AML that will likely result in improved prognostication and development of novel, risk-adapted therapeutic approaches.

Old and new prognostic factors in acute myeloid leukemia with deranged core‐binding factor beta

“…Similarly, regarding the impact on outcome, this research article study showed that KIT mutations did not reach a significative value as independent prognostic factor for relapse and survival neither in the multivariate nor in the Kaplan-Meier analysis, in contrast to those reported in adult patients with t(8;21) (Figs. 1B-2B; Tables III and IV) [24,[26][27][28][30][31][32].…”

Unusual Morphology in A Case of AML With t(8;21):A Diagnostic Dilemma

“…It was the firstcytogenetic abnormality discovered in AML [2]. The t(8;21) abnormality is found in approximately 5%-10% of all AML cases and 10%-22% of AML cases with maturation corresponding to the previous FAB class M2 [3,4,5].t(8;21) is most common in children/younger patients [6]. This type of AML has a high complete remission rate with standard chemotherapy and a prolonged survival when sequential high dose cytarabine was administered [1].Cytogenetically, t(8;21) AML is frequently associated with a loss of the sex chromosome Y in males and inactive X in females [1], which was also found in our case; 3.4% of the cases show variant translocations [1].…”

Distinct Gene Mutations, their Prognostic Relevance and Molecularly Targeted Therapies in Acute Myeloid Leukemia (AML)

“…D816V mutation is associated with a worse prognosis in AML with t(8;21) RUNX1-RUNX1T1, in contrast good prognosis normally linked with t(8;21) [101,102]. In inv(16)/t(16;16), a study by the Cancer and Leukemia Group B on a larger patient cohort showed that KIT mutations are associated with a higher cumulative incidence of relapse, this difference was mainly due to the effect of KIT exon 17 mutations [100].…”