Tribbles homolog 2 (Trib2) and HoxA9 cooperate to accelerate acute myelogenous leukemia.
Trib2 is a member of the Trib family of serine/threonine kinase-like proteins (Trib1, Trib2, Trib3). Mice reconstituted with hematopoietic stem cells (HSC) retrovirally expressing Trib2 uniformly developed fatal transplantable acute myelogenous leukemia (AML). Trib2-induced AML was clonal and we sought to identify cooperating genes in Trib2-induced AML. Using Splinkerette PCR techniques, we identified proviral insertion near HoxA9 in a Trib2 monoclonal tumor, which resulted in greatly elevated HoxA9 expression. Mice reconstituted with HSC cotransduced with HoxA9 and Trib2 had accelerated onset of AML compared to either gene alone. These data identify Trib2 and HoxA9 as cooperating genes in AML.
Keeshan
Karen
K
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Shestova
Olga
O
Ussin
LaShon
L
Pear
Warren S
WS
D000818:Animals; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000473:pathology; D051379:Mice; D015513:Oncogene Proteins; D017346:Protein Serine-Threonine Kinases / Q000008:administration & dosage / Q000494:pharmacology* / Q000037:antagonists & inhibitors; D014161:Transduction, Genetic
D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C097899:homeobox protein HOXA9; C515847:tribbles 2 protein, mouse; D017346:Protein Serine-Threonine Kinases