A role for MEIS1 in MLL-fusion gene leukemia.
Leukemias with MLL rearrangements are characterized by high expression of the homeobox gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplantation recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA-mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.
Kumar
Ashish R
AR
Masonic Cancer Center, Minneapolis, MN 55455, USA.
Li
Quanzhi
Q
Hudson
Wendy A
WA
Chen
Weili
W
Sam
Thien
T
Yao
Qing
Q
Lund
Erik A
EA
Wu
Baolin
B
Kowal
Branden J
BJ
Kersey
John H
JH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D055879:Gene Knock-In Techniques; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D007938:Leukemia / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009368:Neoplasm Transplantation
D018398:Homeodomain Proteins; C497422:KMT2A protein, human; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse