Our data suggest that miR-638 regulates proliferation and myeloid differentiation by targeting CDK2 and may serve as a novel target for leukemia therapy or marker for AML diagnosis and prognosis.
In this study, we have used YAC probes encompassing the CDKN2 locus to analyze by fluorescence in situ hybridization patients with leukemia and lymphoma and translocations involving 9p in order to establish the CDKN2 status in relation to the karyotype.
Recently, two putative tumor suppressor gene(s) CDKN2 and MTS2 have been mapped to the 9p21 region, and shown to be deleted in a large number of tumors including leukemias, melanomas, bladder cancers and brain tumors.
These data show the coexistence of multiple genetic defects in childhood B-lineage ALL Cell lines with t(12;21) will facilitate the study of TEL-AML1 and AML1-TEL fusion proteins as well as TEL and CDKN2 gene inactivation in leukemia transformation and progression.
The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been recently identified as a putative tumor suppressor gene because of the high frequency of homozygous deletion observed in numerous human tumor cell lines, including leukemias.
Finally, of 10 cases of BCP-ALL that produced overt, transplantable leukemia in mice with severe combined immunodeficiency (SCID), seven showed biallelic CDKN2 deletions.