18227349

pubmed:Citation

9

The c-Myb gene encodes a transcription factor required for proliferation and survival of normal myeloid progenitors and leukemic blast cells. Targeting of c-Myb by antisense oligodeoxynucleotides has suggested that myeloid leukemia blasts (including chronic myelogenous leukemia [CML]-blast crisis cells) rely on c-Myb expression more than normal progenitors, but a genetic approach to assess the requirement of c-Myb by p210(BCR/ABL)-transformed hematopoietic progenitors has not been taken. We show here that loss of a c-Myb allele had modest effects (20%-28% decrease) on colony formation of nontransduced progenitors, while the effect on p210(BCR/ABL)-expressing Lin(-) Sca-1(+) and Lin(-) Sca-1(+)Kit(+) cells was more pronounced (50%-80% decrease). Using a model of CML-blast crisis, mice (n = 14) injected with p210(BCR/ABL)-transduced p53(-/-)c-Myb(w/w) marrow cells developed leukemia rapidly and had a median survival of 26 days, while only 67% of mice (n = 12) injected with p210(BCR/ABL)-transduced p53(-/-)c-Myb(w/d) marrow cells died of leukemia with a median survival of 96 days. p210(BCR/ABL)-transduced c-Myb(w/w) and c-Myb(w/d) marrow progenitors expressed similar levels of the c-Myb-regulated genes c-Myc and cyclin B1, while those of Bcl-2 were reduced. However, ectopic Bcl-2 expression did not enhance colony formation of p210(BCR/ABL)-transduced c-Myb(w/d) Lin(-)Sca-1(+)Kit(+) cells. Together, these studies support the requirement of c-Myb for p210(BCR/ABL)-dependent leukemogenesis.

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http://linkedlifedata.com/resource/pubmed/journal/7603509

http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myb

May

pubmed-author:BenderTimothy PTP, pubmed-author:CalabrettaBrunoB, pubmed-author:CorradiniFrancescaF, pubmed-author:LidonniciMaria RosaMR, pubmed-author:WaldronToddT

1

NLM

4771-9

pubmed-meshheading:18227349-Animals, pubmed-meshheading:18227349-Cell Transformation, Neoplastic, pubmed-meshheading:18227349-Fusion Proteins, bcr-abl, pubmed-meshheading:18227349-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:18227349-Hematopoietic Stem Cells, pubmed-meshheading:18227349-Leukemia, pubmed-meshheading:18227349-Mice, pubmed-meshheading:18227349-Mice, Inbred C57BL, pubmed-meshheading:18227349-Neoplasms, Experimental, pubmed-meshheading:18227349-Proto-Oncogene Proteins c-myb, pubmed-meshheading:18227349-Transduction, Genetic

Requirement of c-Myb for p210(BCR/ABL)-dependent transformation of hematopoietic progenitors and leukemogenesis.

Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural