Implicating the bcr/abl gene in the pathogenesis of Philadelphia chromosome-positive human leukemia

George Q. Daley*, Yinon Ben-Neriah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

The hypothesis that the Philadelphia chromosome might have a causative role in human chronic myelogenous leukemia (CML) was validated by the discovery that the human homologue of the v-abl oncogene of Abelson murine leukemia virus (A-MuLV) mapped to chromosome 9q34, precisely the locus disrupted in the formation of the Philadelphia chromosome. The result immediately suggested an etiologic mechanism: the breakpoint of the Philadelphia chromosome might activate the human c-abl homologue to behave as a transforming gene similar to v-abl. The human homologue of a murine leukemia virus oncogene could be activated to play a direct role in the pathogenesis of human leukemia. Deciphering the molecular consequences of the Philadelphia chromosome, translocation has provided substantial evidence to implicate an activated c-abl gene in the etiology of Ph1-positive human leukemia. The presence of a Philadelphia chromosome characterizes the leukemic tissue in over 90% of the patients with chronic myelogenous leukemia. Virtually all of these patients will harbor the molecular hallmark of CML, a detectable rearrangement of the bcr gene in chromosome 22. The c-abl gene can be activated to leukemogenicity by a variety of mechanisms, including fusion with gag sequences, internal deletions, and point mutations.

Original languageAmerican English
Pages (from-to)151-184
Number of pages34
JournalAdvances in Cancer Research
Volume57
StatePublished - 1991

Bibliographical note

Funding Information:
We thank Richard Van Etten, Martin Scott, and Asne Bauskin for critical comments on the manuscript, and Peter K. Jackson, Naomi Rosenberg, and Owen Witte for communicating results prior to publication. Y.B.-N. holds a Career Development Award from the Israel Cancer Research Fund.

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