Additional chromosomal abnormalities and variability of BCR breakpoints in Philadelphia chromosome/BCR-ABL-positive acute lymphoblastic leukemia in Taiwan (original) (raw)
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Leukemia, 2004
Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph þ ) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph þ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or 450 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P ¼ 0.124) and disease-free survival (P ¼ 0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications.
Leukemia Research, 2011
Background: Philadelphia-chromosome positive acute myeloid leukemia (Ph+ AML) is a rare entity and patient prognosis is poor, with short median survival. Biphenotypic acute leukemia (BAL) is a rare disorder that is difficult to diagnose and it displays features of both myeloid and lymphoid lineage. The aim of this study was to highlight the incidence of Philadelphia chromosome and its presence in cases of acute myeloid and biphenotypic leukemia and determine its role in the outcome of these leukemias. Subjects and methods: This study examined 464 subjects with newly diagnosed acute myeloid leukemia: 312 were males and 152 were females. All individuals were subjected to immunophenotyping and conventional karyotyping. FISH was used in failed cases of conventional cytogenetics analysis to quantify disease and to prove positive BCR-ABL fusion gene. Results: the incidence of Ph+ chromosome was found to be higher in BAL (38.4%) than in AML (1.99%). There was statistically significant difference according to the age and the median survival time between the two groups. Conclusion: Detection of specific chimeric transcripts in AML and BAL at the time of diagnosis was crucial since it plays an important role for accurate risk stratification and treatment management.
Blood, 1991
During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph') ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph'/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph'/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, al-TH ADVANCES in the molecular evaluation of W hematologic malignancies, it has been shown that Philadelphia chromosome (Ph')-positive acute lymphoblastic leukemia (ALL) is a heterogeneous group of disorders.'~2 Although the reciprocal translocation between chromosomes 9 and 22 is cytogenetically identical in cases of ALL and chronic myelogenous leukemia (CML), the translocations generally differ at the molecular In cases of CML and some cases of ALL the c-abl proto-oncogene on chromosome 9 joins to a 5.8-kb region on chromosome 22 known as the breakpoint cluster region (bcr), which lies within a larger gene known as BCR.4 This union produces a unique 8.5-kb mRNA and results in a characteristic 210-Kd protein, ~2 1 0 .~~~ However, in other cases of ALL the c-abl proto-oncogene fuses to chromosome 22 within the large BCR gene, but at a region 5' to the bcr, which results in a smaller mRNA transcript and a 190-Kd protein, ~1 9 0. ' ,~ Both p210 and p190 are tyrosine phosphokinases, and, like
Leukemia & lymphoma, 2017
About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.
Philadelphia Chromosome In Acute Lymphoblastic Leukemia
Sohag Medical Journal, 2017
Background. Acute lymphoblastic leukemia (ALL) is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. Philadelphia chromosome (Ph)-positive ALL, a high-risk cytogenetic subset, accounts for 25-30% of adult ALL cases but occurs in less than 5% of children. We aimed with this study to detect Ph chromosome in acute lymphoblastic leukemia patients, using (FISH), and to assess their relation with other standard prognostic factors and therapeutic response. Patients and methods. This study was carried out on 39 newly diagnosed ALL patients. All patients were subjected to; History, clinical examination and Laboratory investigations, which included CBC (Complete Blood Count), P.BL.(Peripheral Blood) smear and BM(Bone Marrow) examination, immunophenotyping and Fluorescence in situ hybridization to detect Ph chromosome. Results. This study was carried out on 39 newly diagnosed ALL patients show: Statistical analysis of patients' t(9;22) with other factors revealed significant association (p<0.05) of t(9;22) with patients outcome, age >35 years, hepatosplenomegaly, absence of lymphadenopathy, TLC ≥50X10 9 /L, absolute P.Bl blasts ≥4.4X10 9 /L and immunophenotyping. Conclusion. Ph chromosome expression serve as a powerful prognostic marker in adulthood ALL, As ph +ve adult acute lymphoblastic leukemia has poor prognosis and can be used as prognostic indicators for therapeutic response.
Genetics and Molecular Biology, 2003
The Philadelphia chromosome is observed in 5% of pediatric acute lymphocytic leukemia (ALL) and in 25% to 50% of adult ALL cases, and is associated with poor prognosis. Double Ph in a hyperdiploid karyotype is common in chronic myeloid leukemia (CML), but rarely found in ALL. We report here the case of a girl diagnosed with ALL at 7 years of age. After treatment with the pediatric protocol BFM 83 for ALL, she stayed in continuous complete remission for nine years. At age 19, she was re-admitted with a white blood cell count of 6.8 x 10 9 /L with 3% blasts, and a platelet count of 65 x 10 9 /L. Bone marrow aspirate showed 92.6% lymphoid blast cells, and chromosome analysis after G-banding revealed the karyotype 51,XX,+?5,t(9;22)(q34.1;q11.2),+16,+20,+21,+der(22)t(9;22)(q34.1;q11.2)[10]/46,XX[1]. FISH analysis for the BCR/ABL fusion showed 56% of interphase cells with two fusion signals, 30% with one, and 6% with three. Double Ph is rare in relapsed leukemia, and the possibility of secondary leukemia cannot be ruled out.
Oncology letters, 2010
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Approximately 84% of cases of ALL are classified as B-precursor ALL, 14% of cases are T-cell and 2% of cases are B-cell (B-)ALL. About one third of B-ALL cases show an abnormal karyotype. Combining data obtained by immunophenotyping, karyotyping and molecular cytogenetic analyses allows for a better understanding of this heterogeneous disease. This study reports an exceptional B-ALL case with a poor prognosis and unique complex chromosomal aberrations not previously observed, i.e., a translocation involving the six chromosomal regions 1q42, 4q21, 4q24, 4q35 (twice), 8q22 and 10p15.3 besides 9q34 and 22q11.2.
Leukemia, 2005
Deletions from the derivative chromosome 9, der(9), of the translocation, t(9;22)(q34;q11), at the site of the ABL/BCR fusion gene, have been demonstrated by fluorescence in situ hybridisation (FISH), in both Philadelphia chromosome (Ph)positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). In CML they occur in 10-15% of cases and appear to indicate a worse prognosis, whereas in ALL, the situation is unclear. This study presents the findings of dual fusion FISH used to detect such deletions in a series of 27 BCR/ ABL-positive childhood ALL patients. Metaphase FISH was essential for the accurate interpretation of interphase FISH signal patterns. Three cases (11%) had a single fusion signal, resulting from deletions of the der(9). Three other patients with variant translocations and one with an insertion, also had a single fusion, but with no evidence of deletions. Gain of a fusion in approximately one-third of patients indicated a second Ph, which appears to be a diagnostic marker of Phpositive ALL. This study shows that the incidence of deletions from the der(9) in childhood ALL is at least as high as that reported for CML.