PMCID: PMC5177472 DOI: 10.1111/bjh.14413
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML.
British journal of haematology
Adolescent; Adult; Aged; Aged, 80 and over; Carrier Proteins; Cell Adhesion Molecules, Neuronal; Child; Child, Preschool; Drug Resistance, Neoplasm; Extracellular Matrix Proteins; Female; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genomics; Humans; Infant; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nerve Tissue Proteins; Nuclear Proteins; Pregnancy; Remission Induction; Repressor Proteins; Serine Endopeptidases; Treatment Failure; Young Adult
cytogenetically normal acute myeloid leukaemia; induction failure; paediatric leukaemia; primary chemoresistance; targeted deep sequencing genomics; AML
Brown, F. C., Cifani, P., Drill, E., He, J., Still, E., Zhong, S., Balasubramanian, S., Pavlick, D., Yilmazel, B., Knapp, K. M., Alonzo, T. A., Meshinchi, S., Stone, R. M., Kornblau, S. M., Marcucci, G., Gamis, A. S., Byrd, J. C., Gonen, M., Levine, R. L., Kentsis, A. Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia. British journal of haematology 176, 86-91 (2017).