Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia.
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ABSTRACT:
SUBMITTER: Shih AH
PROVIDER: S-EPMC4518555 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
Publications
Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia.
Shih Alan H AH Jiang Yanwen Y Meydan Cem C Shank Kaitlyn K Pandey Suveg S Barreyro Laura L Antony-Debre Ileana I Viale Agnes A Socci Nicholas N Sun Yongming Y Robertson Alexander A Cavatore Magali M de Stanchina Elisa E Hricik Todd T Rapaport Franck F Woods Brittany B Wei Chen C Hatlen Megan M Baljevic Muhamed M Nimer Stephen D SD Tallman Martin M Paietta Elisabeth E Cimmino Luisa L Aifantis Iannis I Steidl Ulrich U Mason Chris C Melnick Ari A Levine Ross L RL
Cancer cell 20150401 4
Specific combinations of acute myeloid leukemia (AML) disease alleles, including FLT3 and TET2 mutations, confer distinct biologic features and adverse outcome. We generated mice with mutations in Tet2 and Flt3, which resulted in fully penetrant, lethal AML. Multipotent Tet2(-/-);Flt3(ITD) progenitors (LSK CD48(+)CD150(-)) propagate disease in secondary recipients and were refractory to standard AML chemotherapy and FLT3-targeted therapy. Flt3(ITD) mutations and Tet2 loss cooperatively remodeled ...[more]
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2024-06-03 | PXD050623 | Pride