Additional chromosomal abnormalities and variability of BCR breakpoints in Philadelphia chromosome/BCR‐ABL‐positive acute lymphoblastic leukemia in Taiwan

Ko, Bor-Sheng; Tang, Jih-Lu; Lee, Fen‐Yu; Liu, Ming‐Chi; Tsai, Woei; Chen, Yao‐Chang; Wang, Chiu‐Hwa; Sheng, Ming-Chin; Lin, Dong; Lin, Kai‐Hsin; Tien, Hwei‐Fang

doi:10.1002/ajh.10227

Cited by 31 publications

(22 citation statements)

References 36 publications

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“…[1,6,7]. The t(9;22) translocation, resulting in the Philadelphia (PH) chromosome and the formation of BCR/ABL fusion transcripts, is the most common cytogenetic abnormality occurring in adult precursor B-cell ALL with an incidence of 13-33% in Western studies [1,6,[8][9][10][11][12][13][14][15]. A subset of PH chromosome positive (PH/BCR/ABL?)…”

Section: Introductionmentioning

confidence: 99%

Adult precursor B lymphoblastic leukemia in Shanghai, China: characterization of phenotype, cytogenetics and outcome for 137 consecutive cases

et al. 2009

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Acute lymphoblastic leukemia (ALL) accounts for 20-30% of adult leukemia in the West. However, detailed studies of B-cell-specific ALL in adult Asian populations are lacking. We diagnosed and characterized 137 consecutive cases of precursor B lymphoblastic leukemia (precursor B-cell ALL) presented to our laboratory in Shanghai using the WHO 2001 classification system. Patient clinical, phenotypic and cytogenetic characteristics were correlated with outcome. In contrast to Western studies, females (71) outnumbered males (66) partly due to an increased prevalence of the CD10- pro B-cell phenotype. Females with a CD10- pro B-cell phenotype exhibited significantly better overall survival than males. The most common cytogenetic abnormality was the Philadelphia chromosome (PH/BCR/ABL) which was found in approximately 37% of the cases. Cases of precursor B cell ALL lacking the PH/BCR/ABL genotype exhibited a pronounced age-dependent, gender prevalence with a modal age in the sixth decade for females compared to the second decade for males. These findings suggest significant geographic heterogeneity in precursor B-cell ALL which may be of both etiological and therapeutic significance.

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Section: Introductionmentioning

confidence: 99%

Adult precursor B lymphoblastic leukemia in Shanghai, China: characterization of phenotype, cytogenetics and outcome for 137 consecutive cases

et al. 2009

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“…Although the presence of hyperdiploid karyotypes is well known in pediatric acute lymphoblastic leukemia (ALL), and it has been associated with good prognosis, its impact on prognosis is not well defi ned in adult ALL. 19,20 However, hyperdiploidy is a rare cytogenetic abnormality in AML, primarily occurring in de-novo disease in older patients, and it appears to be associated with poor prognosis, 19 which was also verifi ed in our patient. Although the reason that imatinib is not able to eradicate the malignant clone is not known, recent advances in the understanding of cancer and leukemia stem-cell biology, and data about imatinib-resistant CML and BCR-ABLrelated genomic instability have led to the proposal of some mechanisms.…”

Section: Discussionmentioning

confidence: 68%

Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era

et al. 2009

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Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, CD61, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8, 13, 19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response.

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“…In contrast, in chronic myeloid leukemia, the production of protein of 210-KDa (p210 BCR/ABL ) is evident. Patients with either p190 BCR/ABL or p210 BCR/ABL have similar clinical outcome [9]. Furthermore, our patient presented double fusion BCR/ABL1 signal.…”

Section: Discussionmentioning

confidence: 77%

Duplication of Philadelphia chromosome and trisomy of chromosome 21 in a pediatric patient with acute lymphoblastic leukemia

et al. 2010

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The evaluation of molecular and cytogenetic characteristics using novel techniques has significantly contributed into the insight of leukemia. In this study, immunoglobulin heavy chain gene rearrangements (V(H)D(H)J(H) region) were analyzed by polymerase chain reaction (PCR). Point mutations of the D835/I836 in the activation loop (AL) domain of the second tyrosine kinase domain of the fms-related tyrosine kinase 3 (FLT3) gene and NRAS (neuroblastoma cell line) point mutations were also analyzed by PCR. Furthermore, sequence analysis of the V(H)D(H)J(H) region was performed, as well as, chromosomal aberrations were identified by interphase fluorescence in situ hybridization (iFISH) in a 12.5-year-old boy with acute lymphoblastic leukemia. Positive MRD was found in bone marrow samples obtained at various time points during and after treatment completion prior to relapse. Molecular analysis of the FLT3 gene mutations revealed an acquired a G → T mutation at codon 835, which resulted to substitution of aspartate 835 for tyrosine (D835Y). Cytogenetic analysis with iFISH showed t(9;22) (q34;q11.2), with minor-BCR/ABL1 fusion gene in the majority of nuclei, while a subclone with duplication of the Philadelphia chromosome was observed. Triple signals of AML1 were detected in 80% of nuclei, which were compatible with trisomy of chromosome 21. BCR/ABL1 fusion gene, duplication of Philadelphia chromosome and persistence of MRD constitute inferior prognostic factors, while hyperdiploidy, trisomy of chromosome 21 and FLT3-AL mutations are related to better prognosis. The study of cytogenetic and molecular characteristics is essential in order to decide on the optimal treatment protocol in childhood leukemia.

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Additional chromosomal abnormalities and variability of BCR breakpoints in Philadelphia chromosome/BCR‐ABL‐positive acute lymphoblastic leukemia in Taiwan

Cited by 31 publications

References 36 publications

Adult precursor B lymphoblastic leukemia in Shanghai, China: characterization of phenotype, cytogenetics and outcome for 137 consecutive cases

Adult precursor B lymphoblastic leukemia in Shanghai, China: characterization of phenotype, cytogenetics and outcome for 137 consecutive cases

Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era

Duplication of Philadelphia chromosome and trisomy of chromosome 21 in a pediatric patient with acute lymphoblastic leukemia

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