1/20. Expression of the NUP98/HOXA9 fusion transcript in the blast crisis of philadelphia chromosome-positive chronic myelogenous leukaemia with t(7;11)(p15;p15).The t(7;11)(p15;p15) translocation is a recurrent aberration observed in acute myeloblastic leukaemia (AML) and chronic myelogenous leukaemia (CML). It has been shown that the NUP98 gene at 11p15 is fused with the HOXA9 gene at 7p15 in AML with t(7;11). We report the first case with CML expressing the NUP98/HOXA9 fusion transcript. A 27-year-old Japanese man was initially diagnosed as in the chronic phase of Philadelphia-positive CML. At the diagnosis of myeloid blast crisis, the karyotype evolved to 46, XY, t(7;11)(p15;p15), t(9;22)(q34;q11). reverse transcriptase polymerase chain reaction identified the NUP98/HOXA9 transcript, suggesting that the NUP98/HOXA9 fusion protein could play a critical role in the progression to blast crisis.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/20. Triple Philadelphia chromosomes with major-bcr rearrangement in hypotriploid erythroleukaemia.The Philadelphia (Ph) chromosome is observed in approximately 1% of patients with acute myeloblastic leukaemia (AML), especially subtypes M1 and M2 in the French-American-British classification. We describe here a cytogenetic and molecular investigation of a rare case with Ph-positive AML M6 (erythroleukaemia). A 63-yr-old woman was diagnosed as having erythroleukaemia. Leukaemic cells were positive for CD4 and CD7 as well as CD13, CD33, CD34 and HLA-DR. They were analyzed by G-banding, fluorescence in situ hybridization (FISH), Southern blot and reverse transcriptase polymerase chain reaction analyses. The karyotypes at diagnosis were as follows: 61, XX, -X, -1, -2, -3, -4, -5, -7, t(9;22)(q34;q11)x 2, -15, -16, -17, -18, 19, 21, 22 [3]/61, idem, -22, der(22)t(9;22) [36]. FISH with BCR/ABL probes showed that 39% and 57% of interphase nuclei had double and triple BCR/ABL fusion signals, respectively. Chromosome analysis in complete remission showed a normal karyotype in all 20 metaphases, confirming the diagnosis as Ph positive-acute leukaemia. FISH at relapse showed that 92% of interphase nuclei had triple fusion signals. Rearrangement of major breakpoint cluster region (M-bcr) in the BCR gene and coexpression of p210-type (b2a2) and p190-type (e1a2) BCR/ABL fusion transcripts due to alternative splicing were also detected. We conclude that clonal evolution from double to triple Ph chromosomes may be implicated in the disease progression. Considering other two reported cases, Ph-positive erythroleukaemia appears to be correlated with coexpression of myeloid/T-lymphoid markers and hyperdiploidy with double or triple Ph chromosomes, although breakpoints in the BCR gene are heterogenous.- - - - - - - - - - ranking = 145.42293549089keywords = disease progression, progression (Clic here for more details about this article) |
3/20. Philadelphia-positive T-ALL in a patient with follicular lymphoma.Follicular lymphoma is a B cell malignancy prone to transformation into a large cell diffuse histology. This progression may be multi-clonal as determined by IgH rearrangement. Similar multi-clonal occurrences have been described in immunocompromised patients. However, the lymphoma cells remain predominantly of B cell type. Rarely, composite lymphomas with diffuse T cell histology have been reported arising from follicular lymphoma. The development of T cell leukaemia in a patient with a pre-existing B cell malignancy is an extremely rare event. The occurrence of T cell acute lymphoblastic leukaemia (T-ALL) following follicular lymphoma (FL) has not previously been reported. We report a case of Philadelphia positive (Ph ) T cell ALL developing in a patient who previously had FL which may give some insight into the cell of origin and the defects responsible for malignant transformation of the lymphocytes.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
4/20. Coexistence of independent myelodysplastic and philadelphia chromosome positive clones in a patient treated with hydroxyurea.We report a patient with philadelphia chromosome positive (Ph ve) chronic myelogenous leukemia (CML), treated with hydroxyurea alone, who upon disease progression developed an additional Ph - ve clone containing chromosomal abnormalities typical of myelodysplastic syndrome (MDS). Retrospective analysis of a cryopreserved stem cell specimen from diagnosis confirmed that this second clone developed during the course of treatment. The development of a clone with additional cytogenetic abnormalities in CML has only been reported after leukemogenic treatment, stem cell transplantation or interferon. We report a case of secondary Ph - ve MDS/AML during blast crisis in a patient treated with hydroxyurea for CML.- - - - - - - - - - ranking = 145.42293549089keywords = disease progression, progression (Clic here for more details about this article) |
5/20. Genomic deletions on other chromosomes involved in variant t(9;22) chronic myeloid leukemia cases.The Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML) and is observed in more than 90% of CML cases. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22). Deletions adjacent to the translocation junction on the derivative chromosome 9 were recently described by different groups. The deletions may identify a subgroup with a worse prognosis. The presence of similar deletions on the third derivative other than the 9 and 22 chromosomes in CML with variant translocation has never been investigated. We studied three cases of CML variants showing relatively large deletions on the third chromosome involved in the translocation. Known tumor-suppressor genes (TSGs) or genes involved in signal transduction and in the modulation of cell proliferation were found to be located inside these deleted regions. As an alternative to Knudson's two-hit model, the "haplo-insufficiency" hypothesis suggests that the deletion of a single allele of a TSG can play an important role in tumor progression. Our findings suggest that great attention should be paid to the molecular cytogenetic characterization of variant t(9;22) CML patients to unveil fully the biological heterogeneity of CML.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
6/20. Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib.Amplification of the bcr-abl fusion gene has recently been associated with resistance to imatinib therapy in chronic myeloid leukemia (CML). A 55-yr-old man was diagnosed with Philadelphia (Ph) chromosome-positive CML. Resistance to interferon treatment and occurrence of blastic phase lead to the decision of imatinib therapy. After two autologous stem cell transplantation, the patient reverted to chronic phase with a decrease in the proportion of Ph chromosome-positive cells under imatinib. A second blastic phase occurred 4 months after transplantation, of which the patient died. Cytogenetic studies, including fluorescent in situ hybridization, showed a (9;22)(q34;q11) translocation and one bcr-abl fusion gene during the whole evolution, but for the last 2 months. Bcr-abl gene amplification (over 25 copies) was noted while banding cytogenetics showed a karyotype of 55-62 chromosomes with multiple double minutes (dmin). To the best of our knowledge, dmin containing amplified bcr-abl gene has never been reported in patients with CML. Therefore, although we cannot exclude that the gene amplification was strictly associated with disease progression, our data may suggest that the amplification resulted in resistance to imatinib.- - - - - - - - - - ranking = 145.42293549089keywords = disease progression, progression (Clic here for more details about this article) |
7/20. Amplification of the BCR/ABL fusion gene clustered on a masked philadelphia chromosome in a patient with myeloblastic crisis of chronic myelocytic leukemia.Although the chronic phase of chronic myelocytic leukemia (CML) is characterized by the Philadelphia (Ph) chromosome creating a hybrid BCR/ABL gene, additional genetic changes involved in blast crisis are poorly understood. We report a 4-8-fold amplification by tandem duplication of the BCR/ABL fusion gene clustered on a masked Ph chromosome in a 61-year-old male patient with CML in myeloblastic crisis. Our finding suggests that the BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Ph-positive CML.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
8/20. [Late appearance of philadelphia chromosome with the p190 BCR/ABL chimeric transcript in acute myelogenous leukemia progressing from myelodysplastic syndrome]We report a late appearance of the philadelphia chromosome (Ph) with the p190 BCR/ABL chimeric transcript in a 69-year-old patient with acute myelogenous leukemia (AML) that had evolved from myelodysplastic syndrome (MDS). In July 1997, the patient was found to have pancytopenia caused by refractory anemia with excess of blasts, which evolved into AML in 4 months. The leukemic cells were positive for CD13, CD14, CD33, and HLA-DR and had a normal karyotype. The patient achieved a complete remission after combination chemotherapy. However, his leukemia relapsed in November 1999, with the appearance of leukemic cells positive for CD7, CD13, CD34, and HLA-DR with a 46, XY, add (18) (p11) karyotype. The patient failed to achieve the second remission after several courses of intensive chemotherapy. When the number of blastic cells, showing the same surface phenotypes, in the peripheral blood increased drastically in April 2000, chromosomal analysis of leukemic cells revealed a 46, XY, t(9;22) (q34;q11), add(18)(p11) karyotype. The fusion of the BCR and ABL genes was confirmed by fluorescence in situ hybridization analysis, and the reverse transcription-polymerase chain reaction analysis further revealed the presence of the p190 BCR/ABL chimeric transcript. The appearance of the Ph chromosome in the course of MDS transforming to AML is very rare and may be correlated to the disease progression.- - - - - - - - - - ranking = 145.42293549089keywords = disease progression, progression (Clic here for more details about this article) |
9/20. Secondary philadelphia chromosome in a patient with acute lymphoblastic leukemia.We report the case of a patient with acute lymphoblastic leukemia who developed a secondary philadelphia chromosome-positive clone (Ph( )). Although the Ph was not detected at diagnosis with conventional cytogenetic analysis and with molecular methods (reverse transcriptase polymerase chain reaction), the Ph was detected with the same techniques at relapse. This anomaly is usually related to the initiation of the disease, but can be a late event related to progression. We discuss these hypotheses and review the literature.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
10/20. Myeloid/natural killer cell blast crisis representing an additional translocation, t(3;7)(q26;q21) in Philadelphia-positive chronic myelogenous leukemia.We encountered a patient in blast crisis (BC) with chronic myelogenous leukemia (CML) who showed immunophenotypic features similar to those previously described in acute myeloid/natural killer (NK) cell precursor leukemia. The blasts were positive for CD7, CD33, CD34, and CD56. cytogenetic analysis disclosed a philadelphia chromosome (Ph) and t(3;7)(q26;q21). Molecular analysis did not detect any EVI1/CDK6 chimeric transcript generated by t(3;7)(q26;q21), but did indicate overexpression of EVI1, which occurs frequently in progression to myeloid BC in CML. Three cases of myeloid/NK cell precursor BC in CML have been reported, but this case is the first to present with Ph and EVI1 abnormality. These observations suggested that a myeloid/NK cell precursor might have been involved in the Ph-positive clone and have been a target for blastic transformation of CML, although EVI1 expression is not specific for transformation to BC from myeloid/NK lineage.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
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