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Mutational and transcriptomic profiling of acute leukemia of ambiguous lineage reveals obscure but clinically important lineage bias. (Haematologica, Dec 2018)

Lao ZT1, Ding LW2, An O3, Hattori N4, Sun QY3, Tan KT5, Mayakonda A3, Chuan WG6, Madan V3, Lin DC7, Yang H3, Koeffler HP3.

Author information
1Cancer Science Institute of Singapore, National University of Singapore, Singapore.
2Cancer Science Institute of Singapore;
3Cancer Science Institute of Singapore.
4Division of Hematology, Department of Medicine, Showa University, Tokyo, Japan.
5Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts. USA.
6Department of Haematology, Singapore General Hospital, Singapore.
7Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles.

Acute leukemia of ambiguous lineage (ALAL) is a rare group of blood cancers that cannot be clearly classified into either myeloid or lymphoid lineage through traditional immunophenotyping (2016 World Health Organization classification). In this study, we performed exome and transcriptome sequencing of 15 diagnosis/relapse samples to identify mutations of this disease. Remarkably, genes involved in DNA repair pathway were frequently mutated and occurred in 80% of the samples. In addition, well known mutations of hematopoietic neoplasms were found in these samples, such as DNMT3A, RUNX1, NOTCH1 and NRAS. A number of ALAL samples simultaneously harboured mutations of both myeloid and lymphoid neoplasm associated genes, which may explain (at least partially) the mixed lineage phenotype of this abnormality. Our study provides novel insights into this rare leukemic entity which may help to develop a better therapeutic strategy.

Keywords: Cytogenetics and Molecular Genetics; Gene Expression Profiling; adult acute leukemia of ambiguous lineage

PMID: 30514800