Mutational and transcriptomic profiling of acute leukemia of ambiguous lineage reveals obscure but clinically important lineage bias (original) (raw)
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The complexity of genomic mutation dictates the prognosis of acute leukemia with ambiguous lineage
2020
Acute leukemia with ambiguous lineage (ALAL) is a rare and highly aggressive malignancy with limited molecular characterization and therapeutic recommendations. In this study, we retrospectively analyzed 1635 acute leukemia cases in our center from January 2012 to June 2018.The diagnose of ALAL was based on either EGIL or 2016 WHO criteria, a total of 39 patients were included. Four patients diagnosed as acute undifferentiated leukemia (AUL) by both classification systems. The mutations detected in bi-phenotypic acute leukemia enriched in genes related to genomic stability and transcriptional regulation; while AUL cases frequently mutated in genes involved in signaling pathway. Survival analysis of all patients suggested that the prognosis of ALAL was independent of immunophenotype, chromosome karyotype, treatment, but significantly associated with the mutation complexity, also termed numbers of the mutations carried by each patient (Log rank p = 0.009 for progression-free survival ...
BMC Medical Genomics, 2009
The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL) and myeloblastic leukemia (AML), with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes.
Oncotarget, 2018
Mixed phenotype acute leukemia (MPAL) is an uncommon manifestation of acute leukemia. The aim of this study is to further characterize the genetic landscape ofcases of MPAL that fulfill the 2016 World Health Organization (WHO) classification criteria for this entity. We identified 14 cases examined by next generation sequencing (NGS) using 28 (10), 53 (3) or 81 (1) gene panels: 7 cases with a B-cell/myeloid (B/My) immunophenotype, 6 T-cell/myeloid (T/My) immunophenotype, and 1 B-cell/T-cell (B/T) immunophenotype. A total of 25 distinct mutations were identified in 15 different genes in 9/14 (64%) patients.-ITD was the only recurrent mutation in 2 patients. B/My MPAL cases less commonly harbored mutations compared with T/My MPAL cases (43% vs. 100%,= 0.07). In contrast, B/My MPALs more commonly showed a complex karyotype compared to T/My MPALs (71% vs. 17%,= 0.1). With NGS and karyotype combined, most (93%) MPAL cases had mutations or cytogenetic abnormalities. With a median follow-u...
Scientific Reports, 2021
Acute leukemia with ambiguous lineage (ALAL) is a rare and highly aggressive malignancy with limited molecular characterization and therapeutic recommendations. In this study, we retrospectively analyzed 1635 acute leukemia cases in our center from January 2012 to June 2018. The diagnose of ALAL was based on either EGIL or 2016 WHO criteria, a total of 39 patients were included. Four patients diagnosed as acute undifferentiated leukemia (AUL) by both classification systems. Among the patients underwent high-throughput sequencing, 89.5% were detected at least one mutation and the median number of gene mutation was 3 (0–8) per sample. The most frequently mutated genes were NRAS (4, 21%), CEBPA (4, 21%), JAK3 (3, 16%), RUNX1 (3, 16%). The mutations detected in mixed-phenotype acute leukemia (MPAL) enriched in genes related to genomic stability and transcriptional regulation; while AUL cases frequently mutated in genes involved in signaling pathway. The survival analysis strongly sugges...
Postępy Higieny i Medycyny Doświadczalnej
Acute myeloid leukemia (AML) is a clonal disorder that results from errors in proliferation and differentiation of bone marrow stem cells from myeloid lineage. According to the Gilliland “two-hit” model, genes of both groups related to proliferation (e.g., FLT3) and differentiation (e.g., CEBPA) must be mutated for full development of AML. The genetic background of AML is very complicated and varied, from single nucleotide mutations or changes in gene expression to cytogenetic aberrations. The DNA sequencing results enable identification of important gene alterations that occur first and may lead the whole leukemogenesis (driver mutations). Some of them have prognostic significance – that is, they are related to the overall survival (OS), complete remission rate, and event-free survival (EFS). The most common molecular changes in AML are mutations in NPM1, CEBPA, FLT3, and DNMT3A. Alterations in NPM1 gene are associated with a good prognosis but simultaneous mutation in FLT3 may cha...
An updated account on molecular heterogeneity of acute leukemia
American journal of blood research, 2021
The progress in the field of personalized therapy has been the backbone for the improved mortality and morbidity figure in cancer especially with reference to acute leukemia. The same has been supported by evolving research and development in the field of genomics. The newer discoveries of mutations and the account of already discovered mutations have been playing a pivotal role to refine management strategy. Here, in this review, we are giving an account of relevant mutations and their potential role in the pathogenesis of acute leukemia. The article discusses the old and newly discovered mutations in acute myeloid/lymphoblastic leukemia. The various pathways and cross-talks between the mutations have been briefly described to develop insight towards their contributory and consequent role in the neoplastic process. The article is to sensitize the students, clinicians, and researchers towards the recent updates and development in genomics of acute leukemia.