Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases

Robert C. Quackenbush, Gary W. Reuther, Juli P. Miller, Kevin D. Courtney, Warren S. Pear, Ann Marie Pendergast

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The reciprocal translocation between chromosomes 9 and 22 that fuses coding sequences of the Bcr and Abl genes is responsible for a remarkably diverse group of hematologic malignancies. A newly described 230-kd form of Bcr-Abl has been associated with an indolent myeloproliferative syndrome referred to as chronic neutrophilic leukemia. We have cloned the corresponding gene and examined the biologic and biochemical properties of p230 Bcr-Abl after retroviral-mediated gene transfer into hematopoietic cell lines and primary bone marrow cells, p230 Bcr-Abl-expressing 32D myeloid cells were fully growth factor independent and activated similar signal transduction pathways as the well-characterized p210 and p185 forms of Bcr- Abl. In contrast, primary mouse bone marrow cells expressing p230 required exogenous hematopoietic growth factors for optimal growth, whereas p185-and p210-expressing cells were independent of growth factors. The 3 Bcr-Abl proteins exerted different effects on differentiation of bone marrow cells. p185 induced outgrowth of lymphoid precursors capable of tumor formation in immunodeficient mice. In contrast, p210- and p230-expressing bone marrow cells caused limited outgrowth of lymphoid precursors that failed to form tumors in immunodeficient mice. Removal of cytokines and autologous stroma from Bcr-Abl-expressing bone marrow cultures produced the expansion of distinct lineages by the various Bcr-Abl proteins. p185 drove expansion of cytokine-independent lymphoid progenitors, while p210 and p230 generated cytokine-independent monocyte/myeloid cells. These findings suggest that the different Bcr-Abl fusion proteins drive the expansion of different hematopoietic populations, which may explain the association of the various Bcr-Abl oncoproteins with different spectra of human leukemias. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2913-2921
Number of pages9
JournalBlood
Volume95
Issue number9
StatePublished - May 1 2000

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bcr-abl Fusion Proteins
Bone
Bone Marrow Cells
Cells
Intercellular Signaling Peptides and Proteins
Myeloid Cells
Cytokines
Tumors
Leukemia, Neutrophilic, Chronic
Genes
abl Genes
Gene transfer
Chromosomes, Human, Pair 22
Signal transduction
Chromosomes, Human, Pair 9
Oncogene Proteins
Electric fuses
Hematologic Neoplasms
Chromosomes
Monocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases. / Quackenbush, Robert C.; Reuther, Gary W.; Miller, Juli P.; Courtney, Kevin D.; Pear, Warren S.; Pendergast, Ann Marie.

In: Blood, Vol. 95, No. 9, 01.05.2000, p. 2913-2921.

Research output: Contribution to journalArticle

Quackenbush, Robert C. ; Reuther, Gary W. ; Miller, Juli P. ; Courtney, Kevin D. ; Pear, Warren S. ; Pendergast, Ann Marie. / Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases. In: Blood. 2000 ; Vol. 95, No. 9. pp. 2913-2921.
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