| First Author | Zhang J | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 31 | Pages | 19093-103 |
| PubMed ID | 26082490 | Mgi Jnum | J:316241 |
| Mgi Id | MGI:6835234 | Doi | 10.1074/jbc.M115.653154 |
| Citation | Zhang J, et al. (2015) Deficiency of beta Common Receptor Moderately Attenuates the Progression of Myeloproliferative Neoplasm in NrasG12D/+ Mice. J Biol Chem 290(31):19093-103 |
| abstractText | Activating Ras signaling is a major driver in juvenile and the myeloproliferative variant of chronic myelomonocytic leukemia (JMML/MP-CMML). Numerous studies suggest that GM-CSF signaling plays a central role in establishing and maintaining JMML/MP-CMML phenotypes in human and mouse. However, it remains elusive how GM-CSF signaling impacts on JMML/MP-CMML initiation and progression. Here, we investigate this issue in a well characterized MP-CMML model induced by endogenous Nras(G12D/+) mutation. In this model, Nras(G12D/+) hematopoietic stem cells (HSCs) are required to initiate and maintain CMML phenotypes and serve as CMML-initiating cells. We show that the common beta chain of the GM-CSF receptor (betac) is dispensable for Nras(G12D/+) HSC function; loss of betac does not affect the expansion, increased self-renewal, or myeloid differentiation bias in Nras(G12D/+) HSCs. Therefore, betac(-/-) does not abrogate CMML in Nras(G12D/+) mice. However, betac deficiency indeed significantly reduces Nras(G12D/+)-induced splenomegaly and spontaneous colony formation and prolongs the survival of CMML-bearing mice, suggesting that GM-CSF signaling plays an important role in promoting CMML progression. Together, our results suggest that inhibiting GM-CSF signaling in JMML/MP-CMML patients might alleviate disease symptoms but would not eradicate the disease. |
