T-lineage blast crisis of chronic myelogenous leukemia: simple record of 4 cases.

Blast crisis (BC) transformation in chronic myelogenous leukemia (CML) can involve each differentiation lineage of the hematopoietic system, i.e. granulocyte, monocyte, erythrocyte, megakaryocyte, and lymphocyte lineage. The lymphoid blast crisis (BC) leukemia cells usually belong to B-lineage, commonly having the phenotype of Pre-B stage of the B-lineage, in which cell-surface immunoglobulin (sIg) is not yet expressed. In contrast, T-lineage BC of CML is extremely rare. The objective of this study is to describe the fenotype, fusion transcript of bcr-abl, TdT, and cytoplasmic CD3 in T-lineage BC CML cases. Case report study. This report shows a simple summary of 4 cases of T-lineage BC of CML which have been collected in the phenotypic and genotypic analysis study for 17 years (1987-2004). In all cases, the chromosomal analysis revealed the presence of t(9;22)(q34;q11) at presentation. Cell surface analysis were done at diagnosis. Cases’ mononuclear cells stored as 10% DMSO were retrieved to be performed reverse transcription (RT) PCR BCR-ABL multiplex to demonstrate the presence of the fusion transcript of bcr-abl. RT-PCR was also performed for detecting the expression of cytoplasmic CD3ε and terminal deoxynucleotydil transferase (TdT). The results of cell surface antigen (CSA) at presentation showed that 1 case was CD7+, CD5-, and CD2-; 1 case CD7+, CD5+, and CD2-; and 2 cases CD7+, CD5+ and CD2+ indicating that all these T-lineage BC of CML cells show the phenotype of pre-(pro-) thymic stage phenotype. In the present study, two cases showed b2a2, one e1a2, and one negative bcr-abl transcript. The RT-PCR revealed the presence of CD3ε mRNA in all cases, and TdT mRNA in only one case. These results can constitute a basis for the future analysis of T-lineage BC of CML from now on.

Retrospective Analysis of Prognostic Factors Affecting Survival After Onset of Blastic Crisis of Chronic Myeloid Leukemia Especially Focused on FAB Classification / 대한혈액학회지

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a progressive course outlined by the transition from the chronic phase (CP) to blastic crisis (BC). The course of CML-BC is still fatal, and in spite of various efforts in treatment, median survival remains short. The aim of the present study was to analyze the prognostic factors having an impact on response to treatment and survival in patients with CML-BC. We also investigated prognostic influence on survival in myeloid BC according to FAB classification. METHODS: All patients (N=35) with CML with onset of CML-BC between January 1992 and May 2002 were reviewed. RESULTS: The median survival for all patients after onset of CML-BC was 7 weeks, and probable survival rate at 24 months was 5.9%. The adverse prognostic factors for survival of CML-BC were high and intermediate risk of Hasford score at diagnosis of CML (P=0.05), normal serum LDH (P=0.016), bone marrow blasts > or =60% (P=0.092), no treatment at CML-BC (P=0.0056), platelet count <20x10(9)/L (P=0.13). Clonal evolution at diagnosis of CML-BC was associated with a shorter survival. Especially in our study, FAB subtype M4-7 (median survival, 4 weeks; 95% CI, 2~6) had shorter survival duration than M0-2 (median survival, 16 weeks; 95% CI, 5~27) in patients with myeloid CML-BC. CONCLUSION: The management of patients with CML-BC remains highly unsatisfactory. Once blast crisis has occurred, there are useful parameters to assess the prognosis for the individual patient and these may be of interest in planning therapy. Our experience suggests that FAB classification M4-7 are poor prognostic factor in patients with myeloid CML-BC.

Detection of p53 Mutant and isochromosome 17q in Myelodysplastic Syndromes and Leukemias / 대한임상병리학회지

BACKGROUND: The p53 gene is a tumor suppressor gene situated in the short arm of chromosome 17(in 17p13 band). The p53 mutation is often correlated with the worsening or relapsing of the hematologic malignancies, and the loss of the short arm of chromosme 17 is associated with a p53 mutation on the remaining allele in several hematologic malignancies. In this study, we investigated correlations between cytogenetic rearrangements leading to 17p deletion, the presence of mutant p53 protein and single strand conformational polymorphism analysis of the p53 gene in myelodysplastic syndromes and leukemias. METHODS: In this study, we analyzed 60 patients with different hematologic malignancies, including 26 acute myelogenous leukemia, 16 acute lymphoblastic leukemia, 7 myelodysplastic syndrome, and 11 chronic myelogenous leukemia. Cytogenetic analysis of the bone marrow was performed by using the G-banding method. Mutant p53 protein was detected using a mouse monoclonal antibody, which reacts with mutant p53. The Polymerase chain reaction and the single strand conformational polymorphism analysis(PCR-SSCP) of exons 5 to 8 of the p53 gene were performed on only 20 patients with acute myelogenous leukemia. RESULTS: Only 1(1.7%) out of 61 patients showed a deletion of the short arm of chromosome 17 through isochromosome 17q and mutant p53 protein. This patient with chronic myelogenous leukemia underwent a clinical transition from chronic to blastic phase. But, PCR-SSCP of the p53 gene was not performed on this patient with isochromosome 17q and mutant p53 protein. CONCLUSIONS: Even though analysis of the p53 gene by PCR-SSCP was not fully performed, this report suggests that the frequency of p53 mutant may be rare in Korean patients with myelodysplastic syndromes and leukemias. In addition, further investigation is required for the correlation between immunofluorescence and PCR-SSCP to detect p53 mutations.