No abstract available.
B-Lymphocytes ; Blast Crisis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

No abstract available.
Blast Crisis* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Megakaryocyte Progenitor Cells*

Chronic myeloid leukemia (CML) is a myeloproliferative disorder, characterized by excessive proliferation of myeloid cells. CML patients in early phase [also known as chronic phase (CP)] usually respond to treatment with tyrosine kinase inhibitors (TKI), some patients respond initially to TKI, but later become resistant, then resulting in the transformation from CP to more advanced phase, which were subclassified as either accelerated phase or blastic phase. At present, the molecular mechanisms of CML have been not yet clear, and acute transformation has been not fully understood, studies have shown that genomic instability promotes the acute conversion of CML. This review discusses the molecular mechanisms leading to the transformation of CML, and some therapeutic approaches.
Blast Crisis ; Drug Resistance, Neoplasm ; Genomic Instability ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Chronic myeloid leukemia is a myeloproliferative disorder characterized by excessive cloning of bone marrow multipotent stem cells. According to the disease course, the CML may be divided into chronic phase (CP), accelerated phase (AP) and blastic phase (BP). At present, the molecular mechanisms of acute transformation of CML has not been fully understood. The recent studies have shown that the epigenetics is one of mechanisms in blastic transformation of CML, including three molecular mechanisms such as DNA modification, histone modifications and RNA-related dysregulation. The molecular mechanisms for epigenetics leading to the transformation of CML are discussed in this review.
Blast Crisis ; genetics ; Disease Progression ; Epigenesis, Genetic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics

Adult ; Blast Crisis ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; complications ; diagnosis ; Ulcer ; diagnosis ; etiology

Atypical chronic myelogenous leukemia (aCML) has dysplastic as well as proliferative features in most instance and rarely evolves to blast crisis, so it is considered as a distinct clinical entity to classical BCR-ABL (+) CML. We experienced a patient who are diagnosed aCML and transformed to myeloid blast crisis after 17 months. Monosomy 7 and deletion of 12p were found on conventional cytogenetics.
Blast Crisis* ; Cytogenetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Monosomy

Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors

OBJECTIVES: To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression. METHODS: An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported. RESULTS: This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period. CONCLUSION These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.
Blast Crisis ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Clonal Evolution ; Disease Progression ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

The blast phase in chronic myelogenous leukemia (CML) is associated with mutation of several genes. It is well known that p53 gene mutation plays a key role in the myeloid or lymphoid blast phase of CML. But for the case of the N-ras gene, the association between N-ras mutations and the blast phase of CML is not yet known. We report here on a case of detecting N-ras point mutation without p53 mutation in a 64 year-old man who suffered from the lymphoblastic blast phase of CML.
Blast Crisis ; Genes, p53 ; Genes, ras ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Point Mutation ; Stress, Psychological

BACKGROUND: Imatinib mesylate, the tyrosine kinase activity of the BCR-ABL fusion gene, induces a remarkable remission in chronic myeloid leukemia (CML) patients. However, resistance to imatinib has been observed in a significant proportion of subjects, with the point mutations of the BCR-ABL kinase domain clinically identified as a possible mechanism. The aim of this study was to investigate clinical resistance to imatinib in Korean CML patients, and search for the point mutation of the BCR-ABL gene. METHODS: The clinical data and cytogenetic results of thirty two CML patients, who were treated with imatinib, between Jan. 2002 and Aug. 2003, were evaluated. Mutational analyses for the point mutations of the BCR-ABL kinase domain in clinically resistant patients were tested using RT-PCR and direct sequencing methods. RESULTS: Complete hematological remission was obtained in all CML patients with a chronic phase and in 4 of 6 CML with accelerated or blast crisis. However, 4 patients (2 in the chronic phase and 2 with blast crisis) relapsed to blast crisis following continued treatment. A major cytogenetic response was observed in 67% of the chronic phase patients, but in 2, the Philadelphia chromosomes reemerged in a follow-up chromosome study. Mutational analyses showed point mutations in the 351st amino acid of the BCR-ABL kinase domain in 2 patients: M351T, which has previously been reported in many studies, and a novel substitution, M351L. CONCLUSION: The frequency of imatinib resistance in Koreans was similar to that found in well-controlled western studies. Point mutations of the BCR-ABL kinase domain were detected in two patients. Further studies, with more sensitive methods and a greater number of patients will help reveal other mechanisms of imatinib resistance and establish more effective treatment plans.
Blast Crisis ; Cytogenetics ; Follow-Up Studies ; Fusion Proteins, bcr-abl ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Mesylates ; Phosphotransferases ; Point Mutation ; Protein-Tyrosine Kinases* ; Tyrosine* ; Imatinib Mesylate