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Haematologica. 2018 Dec 4. pii: haematol.2018.202911. doi: 10.3324/haematol.2018.202911. [Epub ahead of print]

Mutational and transcriptomic profiling of acute leukemia of ambiguous lineage reveals obscure but clinically important lineage bias.

Author information

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

Abstract

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
DOI:
10.3324/haematol.2018.202911
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