Abstract:
:The Ras signal transduction pathway is often deregulated in human myeloid leukaemia. For example, activating point mutations in RAS genes are found in some patients with juvenile chronic myelogenous leukaemia (JCML), while other patients with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase activating protein. By generating mice whose haematopoietic system is reconsituted with Nf1 deficient haematopoietic stem cells we show that Nf1 gene loss, by itself, is sufficient to produce the myeloproliferative symptoms associated with human JCML. We also provide evidence to indicate that Nf1 gene loss induces myeloproliferative disease through a Ras-mediated hypersensitivity to granulocyte/macrophage-colony stimulating factor (GM-CSF). Finally, we describe a genetic screen for identifying genes that cooperate with Nf1 gene loss during progression to acute myeloid leukaemia.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Largaespada DA,Brannan CI,Jenkins NA,Copeland NGdoi
10.1038/ng0296-137subject
Has Abstractpub_date
1996-02-01 00:00:00pages
137-43issue
2eissn
1061-4036issn
1546-1718journal_volume
12pub_type
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