Concomitant with the inhibition of JAK2V617F activity, hypoxia increased the expression of p27/KIP1, the primary negative regulator of the cell cycle, and inhibited cell cycle progression in JAK2V617F-positive leukemia cell lines.
Leukemia progression was associated with increased Bcl-2 expression and cell viability, reduced p27(Kip1) expression, and decreased cell-cycle progression.
To gain further insights into the relevant mechanisms and to detect possible functional differences between both proteins, we conditionally expressed p21(Cip1) and p27(Kip1) in K562, a multipotent human leukemia cell line.
Methylation changes of the CpG islands in the ETV6-CDKN1B interval were assessed by Southern analysis for leukemia patients with hemizygous 12p deletions.
RT-PCR/SSCP (single strand conformation polymorphism) analysis of p27Kip1 cDNA indicated that there was no mutation resulting in amino-acid substitution in 10 feline leukemia and lymphoma cases.
RT-PCR/SSCP (single strand conformation polymorphism) analysis of p27Kip1 cDNA did not uncover any amino acid substitutions in the 10 feline leukemia and lymphoma cases that were examined.
In addition, the putative loss of wild-type function of CDKN1B and ETV6 could indicate a synergistic effect of both genes in the pathogenesis of this leukemia case.
Using a combination of somatic cell hybrid panels and fluorescence in situ hybridization p27Kip1 has been mapped to the short arm of chromosome 12 at the 12p12-12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesotheliomas.