PMID- 9309115 OWN - NLM STAT- MEDLINE DCOM- 19971015 LR - 20190816 IS - 0165-4608 (Print) IS - 0165-4608 (Linking) VI - 98 IP - 1 DP - 1997 Oct 1 TI - p53 loss and point mutations are associated with suppression of apoptosis and progression of CML into myeloid blastic crisis. PG - 28-35 AB - A longitudinal investigation using fluorescence in situ hybridization (FISH) analysis, PCR-SSCP, and in situ detection of apoptosis by the terminal deoxynucleotidyl Transferase (TdT) method was carried out on 13 chronic myelogenous leukemia (CML) patients to study the p53 gene behavior and the apoptotic process during the course of the disease. At diagnosis, FISH showed no loss of the p53 gene on interphase nuclei, and no point mutation was detected by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and sequencing. During the disease course, FISH analysis showed a significative loss of allele (LOA) rate for the p53 gene in eight patients that in seven cases was associated with a suppression of apoptotic process and the progressive expansion of the p53+/p53- clone. DNA sequencing showed in two of these eight patients a point mutation on the other allele, consisting in the formation of a stop codon in one case, and in a frameshift mutation in the other. Six patients had a myeloid blastic crisis (BC), five a lymphoid BC, and the other two an erythroid and an undifferentiated BC, respectively. All patients with myeloid BC and the one with undifferentiated BC disclosed a progressive expansion of the clone with p53 loss that was associated with a significant reduction in apoptosis. On the contrary in the 5 patients with lymphoid BC no significant p53 LOA rate was observed during the course of the disease. In these patients apoptotic process also persisted in the acute phase although in a lower rate as compared to CP. FAU - Stuppia, L AU - Stuppia L AD - Instituto di Biologia e Genetica, Universita di Chieti, Italy. FAU - Calabrese, G AU - Calabrese G FAU - Peila, R AU - Peila R FAU - Guanciali-Franchi, P AU - Guanciali-Franchi P FAU - Morizio, E AU - Morizio E FAU - Spadano, A AU - Spadano A FAU - Palka, G AU - Palka G LA - eng PT - Journal Article PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 SB - IM MH - Adolescent MH - Adult MH - Aged MH - Apoptosis/*genetics MH - Blast Crisis/*genetics MH - DNA Fragmentation MH - Female MH - *Gene Deletion MH - *Genes, p53 MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/pathology/therapy MH - Male MH - Middle Aged MH - *Point Mutation MH - Treatment Outcome EDAT- 1997/10/06 00:00 MHDA- 1997/10/06 00:01 CRDT- 1997/10/06 00:00 PHST- 1997/10/06 00:00 [pubmed] PHST- 1997/10/06 00:01 [medline] PHST- 1997/10/06 00:00 [entrez] AID - S016546089600413X [pii] AID - 10.1016/s0165-4608(96)00413-x [doi] PST - ppublish SO - Cancer Genet Cytogenet. 1997 Oct 1;98(1):28-35. doi: 10.1016/s0165-4608(96)00413-x.