BCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome positive leukemias

Dan Jones, Rajyalakshmi Luthra, Jorge Cortes, Deborah Thomas, Susan O'Brien, Carlos Bueso-Ramos, Seema Hai, Farhad Ravandi, Marcos De Lima, Hagop Kantarjian, Jeffrey L. Jorgensen

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

It remains unresolved how different BCR-ABL transcripts differentially drive lymphoid and myeloid proliferation in Philadelphia chromosome-positive (Ph +) leukemias. We compared BCR-ABL transcript type and level with kinase domain (KD) mutation status, genotype, and phenotype in 1855 Ph + leukemias. Compared with e1a2/p190 BCR-ABL cases, de novo e13-e14a2/p210 Ph + lymphoid leukemia more frequently showed CML-type back-ground, had higher blast-normalized BCR-ABL transcript levels, and more frequent persistent BCR-ABL transcript in the absence of detectable lymphoblasts. Secondary lymphoid blast transformation of CML was exclusively due to e13/e14a2/ p210 BCR-ABL but was associated, at a much higher level than p210 myeloid transformation, with acquisition of new KD mutations and/or Ph genomic amplification. In contrast, myeloid blast transformation was more frequently accompanied by new acquisition of acute myeloid leukemia-type chromosomal aberrations, particularly involving the EVI1 and RUNX1 loci. Therefore, higher kinase activity by mutation, transcriptional up-regulation or gene amplification appears required for lymphoid transformation by p210 BCR-ABL.

Original languageEnglish (US)
Pages (from-to)5190-5192
Number of pages3
JournalBlood
Volume112
Issue number13
DOIs
StatePublished - Dec 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Jones, D., Luthra, R., Cortes, J., Thomas, D., O'Brien, S., Bueso-Ramos, C., Hai, S., Ravandi, F., De Lima, M., Kantarjian, H., & Jorgensen, J. L. (2008). BCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome positive leukemias. Blood, 112(13), 5190-5192. https://doi.org/10.1182/blood-2008-04-148791