Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia

Autoři	JONES Letetia WEI Guangwei ŠEVČÍKOVÁ Sabina PHAN Vernon JAIN Sachi SHIEH Angell WONG Jasmine C. Y. LI Min DUBANSKY Joshua MAUNAKEA Mei Lin OCHOA Rachel ZHU George TENNANT Thelma R. SHANNON Kevin M. LOWE Scott W. LE BEAU Michelle M. KOGAN Scott C.
Rok publikování	2010
Druh	Článek v odborném periodiku
Časopis / Zdroj	The Journal of Experimental Medicine
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Obor	Onkologie a hematologie
Popis	Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia (AML). It has been hypothesized that gain of the MYC protooncogene is of central importance in trisomy 8, but the experimental data to support this are limited and controversial. In a mouse model of promyelocytic leukemia in which the MRP8 promoter drives expression of the PML-RARA fusion gene in myeloid cells, a Myc allele is gained in approximately two-thirds of cases as a result of trisomy for mouse chromosome 15. We used this model to test the idea that MYC underlies acquisition of trisomy in AML. We used a retroviral vector to drive expression of wild-type, hypermorphic, or hypomorphic MYC in bone marrow that expressed the PML-RARA transgene. MYC retroviruses cooperated in myeloid leukemogenesis and suppressed gain of chromosome 15. When the PML-RARA transgene was expressed in a Myc haploinsufficient background, we observed selection for increased copies of the wild-type Myc allele concomitant with leukemic transformation. In addition, we found that human myeloid leukemias with trisomy 8 have increased MYC. These data show that gain of MYC can contribute to the pathogenic effect of the most common trisomy of human AML.