Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891336182> ?p ?o ?g. }
- W2891336182 endingPage "2066" @default.
- W2891336182 startingPage "2053" @default.
- W2891336182 abstract "Abstract Although the pathogenesis of primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs) is linked to constitutive activation of the JAK-STAT pathway, JAK inhibitors have neither curative nor MPN-stem cell-eradicating potential, indicating that other targetable mechanisms are contributing to the pathophysiology of MPNs. We previously demonstrated that Abelson interactor 1 (Abi-1), a negative regulator of Abelson kinase 1, functions as a tumor suppressor. Here we present data showing that bone marrow-specific deletion of Abi1 in a novel mouse model leads to development of an MPN-like phenotype resembling human PMF. Abi1 loss resulted in a significant increase in the activity of the Src family kinases (SFKs), STAT3, and NF-κB signaling. We also observed impairment of hematopoietic stem cell self-renewal and fitness, as evidenced in noncompetitive and competitive bone marrow transplant experiments. CD34+ hematopoietic progenitors and granulocytes from patients with PMF showed decreased levels of ABI1 transcript as well as increased activity of SFKs, STAT3, and NF-κB. In aggregate, our data link the loss of Abi-1 function to hyperactive SFKs/STAT3/NF-κB signaling and suggest that this signaling axis may represent a regulatory module involved in the molecular pathophysiology of PMF." @default.
- W2891336182 created "2018-09-27" @default.
- W2891336182 creator A5000601713 @default.
- W2891336182 creator A5001420554 @default.
- W2891336182 creator A5002550316 @default.
- W2891336182 creator A5006718110 @default.
- W2891336182 creator A5010292765 @default.
- W2891336182 creator A5016218082 @default.
- W2891336182 creator A5018474393 @default.
- W2891336182 creator A5020964256 @default.
- W2891336182 creator A5026630563 @default.
- W2891336182 creator A5028702075 @default.
- W2891336182 creator A5039693085 @default.
- W2891336182 creator A5040395153 @default.
- W2891336182 creator A5043616851 @default.
- W2891336182 creator A5046772202 @default.
- W2891336182 creator A5054655858 @default.
- W2891336182 creator A5056912647 @default.
- W2891336182 creator A5058210944 @default.
- W2891336182 creator A5061074250 @default.
- W2891336182 creator A5061884803 @default.
- W2891336182 creator A5063805112 @default.
- W2891336182 creator A5065223581 @default.
- W2891336182 creator A5067091290 @default.
- W2891336182 creator A5078608377 @default.
- W2891336182 creator A5083157531 @default.
- W2891336182 creator A5083327846 @default.
- W2891336182 creator A5085462251 @default.
- W2891336182 date "2018-11-08" @default.
- W2891336182 modified "2023-10-18" @default.
- W2891336182 title "Bone marrow–specific loss of ABI1 induces myeloproliferative neoplasm with features resembling human myelofibrosis" @default.
- W2891336182 cites W1512355975 @default.
- W2891336182 cites W1881732534 @default.
- W2891336182 cites W1964895626 @default.
- W2891336182 cites W1966740251 @default.
- W2891336182 cites W1970213932 @default.
- W2891336182 cites W1972420606 @default.
- W2891336182 cites W1973431602 @default.
- W2891336182 cites W1979504896 @default.
- W2891336182 cites W1980568348 @default.
- W2891336182 cites W1991035113 @default.
- W2891336182 cites W2001189096 @default.
- W2891336182 cites W2018254868 @default.
- W2891336182 cites W2025592929 @default.
- W2891336182 cites W2030592815 @default.
- W2891336182 cites W2037782111 @default.
- W2891336182 cites W2038195476 @default.
- W2891336182 cites W2038748252 @default.
- W2891336182 cites W2038970416 @default.
- W2891336182 cites W2041386911 @default.
- W2891336182 cites W2044022499 @default.
- W2891336182 cites W2044227662 @default.
- W2891336182 cites W2045959681 @default.
- W2891336182 cites W2049145190 @default.
- W2891336182 cites W2049965335 @default.
- W2891336182 cites W2050757349 @default.
- W2891336182 cites W2055096888 @default.
- W2891336182 cites W2056777053 @default.
- W2891336182 cites W2057650885 @default.
- W2891336182 cites W2057748282 @default.
- W2891336182 cites W2062400136 @default.
- W2891336182 cites W2066080195 @default.
- W2891336182 cites W2067362444 @default.
- W2891336182 cites W2068604152 @default.
- W2891336182 cites W2078743099 @default.
- W2891336182 cites W2078776487 @default.
- W2891336182 cites W2081107312 @default.
- W2891336182 cites W2082732339 @default.
- W2891336182 cites W2083903970 @default.
- W2891336182 cites W2086626683 @default.
- W2891336182 cites W2093034516 @default.
- W2891336182 cites W2094457899 @default.
- W2891336182 cites W2096057003 @default.
- W2891336182 cites W2100196390 @default.
- W2891336182 cites W2105099673 @default.
- W2891336182 cites W2107398329 @default.
- W2891336182 cites W2115351357 @default.
- W2891336182 cites W2116878961 @default.
- W2891336182 cites W2121743767 @default.
- W2891336182 cites W2121956402 @default.
- W2891336182 cites W2124004452 @default.
- W2891336182 cites W2124789340 @default.
- W2891336182 cites W2134835707 @default.
- W2891336182 cites W2138709799 @default.
- W2891336182 cites W2142654480 @default.
- W2891336182 cites W2143668961 @default.
- W2891336182 cites W2147155903 @default.
- W2891336182 cites W2153220877 @default.
- W2891336182 cites W2157942810 @default.
- W2891336182 cites W2159595282 @default.
- W2891336182 cites W2230798701 @default.
- W2891336182 cites W2332087904 @default.
- W2891336182 cites W2344384041 @default.
- W2891336182 cites W2406971307 @default.
- W2891336182 cites W2566942178 @default.
- W2891336182 cites W2590762874 @default.
- W2891336182 cites W2624852477 @default.
- W2891336182 cites W2707568461 @default.