Oncology Medical News about leukemogenesis;RasGRP4

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Possible involvement of RasGRP4 in leukemogenesis
International Journal of Hematology, 04/27/09

Watanabe-Okochi N et al. – Study identifies RasGRP4 (an activator of Ras) as a gene potentially involved in leukemogenesis and it is suggested that RasGRP4 cooperates with AML1 mutations in T cell leukemogenesis as a class I mutation.

Methods

Aim was to understand the molecular mechanism of leukemogenesis: progression of myelodysplastic syndrome (MDS) to acute leukemia
cDNA libraries were constructed from the samples of pts
They were screened by expression-cloning to detect class I mutations that render HF6 cells factor-independent
In vivo effect of RasGRP4 was investigated in a mouse bone marrow transplantation (BMT) model
To study the effect of combination of class I and II mutations on leukemic transformation, mouse BMT model was used in which both AML1 mutant (S291fsX300) and RasGRP4 were transduced into bone marrow cells

Results

RasGRP4 was found to be a candidate for class I mutation in 3 of 6 pts
C57BL/6J mice transplanted with RasGRP4-transduced primary bone marrow cells died of:
- T cell leukemia
- myeloid leukemia, or
- myeloid leukemia with T cell leukemia
Double transduction led to early onset of T cell leukemia but not of AML vs transduction of RasGRP4 alone

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