Acute lymphoblastic leukemia (ALL)

Ido Paz-Priel, Alan D. Friedman

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

It is estimated that 5760 new cases of acute lymphoblastic leukemia (ALL) will be diagnosed in 2013 (including 3509 children younger than 20 years), and 1400 patients will die from this disease(1). Genetically, ALL is one of the better-characterized malignancies, and common recurrent abnormalities are recognized and integrated into the risk stratification. BCR–ABL1 Approximately 20–30% of adult cases of ALL are associated with the reciprocal translocation t(9;22)(q34, q11), or Philadelphia chromosome (Ph; 2,3) This translocation results in a head-to-tail fusion of the ABL1 proto-oncogene on chromosome 9 to the 5ʹ half of the breakpoint cluster region (BCR) from chromosome 22. The resulting chimeric BCR–ABL1 gene is expressed as a 210 or 190 kDa protein. The p190 product is common in ALL, while the p210 is characteristic of chronic myeloid leukemia (4). The N-terminus of the ABL1 kinase is the “Cap” region, which binds to the kinase domain and keeps the Src-homology-2 (SH2) and SH3 autoinhibitory structure in place, thus displacing catalytic residues from the active site and diminishing ATP accessibility (i.e. “off state”; 5,6). In contrast, the chimeric BCR–ABL1 protein is a constitutive kinase that activates the RAS, PI3K/AKT, MEK/ERK, and c-Jun/N-terminal kinase (JNK) pathways, and up-regulates the anti-apoptotic Bcl-2 and Bcl-X, overall resulting in enhanced cell proliferation and survival (7–10).

Original languageEnglish (US)
Title of host publicationMolecular Oncology
Subtitle of host publicationCauses of Cancer and Targets for Treatment
PublisherCambridge University Press
Pages777-785
Number of pages9
ISBN (Electronic)9781139046947
ISBN (Print)9780521876629
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Paz-Priel, I., & Friedman, A. D. (2015). Acute lymphoblastic leukemia (ALL). In Molecular Oncology: Causes of Cancer and Targets for Treatment (pp. 777-785). Cambridge University Press. https://doi.org/10.1017/CBO9781139046947.072