PubMed1998
The occurrence of acute transformation during the treatment of chronic myeloid leukemia (CML) is still a poorly understood mechanism. In this disease p53, p16INK4A, p15INK4B, p57KIP2 mutations and p15INK4B/p16INK4A homo/hemizygous deletions were analyzed in the initial diagnosis phase and during the treatment phase of twelve CML cases, in order to establish whether there was a consistent molecular genetic alteration in its progression. During the treatment period, four of twelve cases had blastic crisis. All the mutations observed in p53, p16INK4A and p15INK4B cumulated in three out of four CML cases who had blastic crises. In one case, p53 codon 282 mutation (CGG-->TGG; arg-->trp) were observed in initial diagnosis. Seven months later, G-->C transition in the 3' side of p15 cDNA (778. nucleotide) was observed in the accelerated phase with the same p53 codon 282 mutation. Thirteen months later, this patient died as a result of blastic crisis. The patient in blastic crises in the initial diagnosis phase had a mis-sense point mutation in p16 codon 69 (ACT-->AGT; thr-->ser) and a polymorphism in codon 68 (GCC-->GCG). Six months later, this patient also died. In one case, p53 codon 237 mutation (ATG-->ATA; met-->ile) were observed in the initial diagnosis phase. Then months later, the patient died as a result of blastic crises. No p15INK4B/p16INK4A homo/hemizygous deletion and p57KIP2 gene mutation which was described in the same pathway were observed in CML progression. These results indicate that p15INK4B and p16INK4A gene alterations may have an affect on the progression of CML-like p53 mutation. A correlation was found with the progression of CML and p53, p15INK4B and p16INK4A somatic mutations. Finding p15INK4B and p16INK4A gene alteration as well as p53 mutations may be a prognostic marker in patients with CML.