Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes.
Koichi TakahashiFeng WangKiyomi MoritaYuanqing YanPeter HuPei ZhaoAbdallah Abou ZharChang Jiun WuCurtis GumbsLatasha LittleSamantha TippenRebecca ThorntonMarcus CoyleMarisela MendozaErika ThompsonJianhua ZhangCourtney D DiNardoNitin JainFarhad RavandiJorge E CortesGuillermo Garcia-ManeroSteven KornblauMichael AndreeffElias JabbourCarlos Bueso-RamosAkifumi Takaori-KondoMarina KonoplevaKeyur PatelHagop KantarjianP Andrew FutrealPublished in: Nature communications (2018)
Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by leukemic blasts presenting myeloid and lymphoid markers. Here we report data from integrated genomic analysis on 31 MPAL samples and compare molecular profiling with that from acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B-ALL), and T cell acute lymphoblastic leukemia (T-ALL). Consistent with the mixed immunophenotype, both AML-type and ALL-type mutations are detected in MPAL. Myeloid-B and myeloid-T MPAL show distinct mutation and methylation signatures that are associated with differences in lineage-commitment gene expressions. Genome-wide methylation comparison among MPAL, AML, B-ALL, and T-ALL sub-classifies MPAL into AML-type and ALL-type MPAL, which is associated with better clinical response when lineage-matched therapy is given. These results elucidate the genetic and epigenetic heterogeneity of MPAL and its genetic distinction from AML, B-ALL, and T-ALL and further provide proof of concept for a molecularly guided precision therapy approach in MPAL.
Keyphrases
- acute myeloid leukemia
- genome wide
- allogeneic hematopoietic stem cell transplantation
- acute lymphoblastic leukemia
- dna methylation
- single cell
- copy number
- dendritic cells
- gene expression
- bone marrow
- machine learning
- stem cells
- single molecule
- immune response
- cell fate
- young adults
- cell therapy
- data analysis
- clinical evaluation