1/32. Smoldering acute myelogenous leukemia in the elderly.Out of 75 consecutive elderly AML patients who did not receive anti-leukemic treatment (52 pts) or failed to respond to differentiating agent (23 pts), 6 patients had survivals of 13.2 to 98 months with treatment restricted to supportive care. This cut-point is far longer than the median survival of the 235 elderly patients (3.5 mo.), either untreated (med. survival: 1 mo.) or treated (with treatment ranging from conventional induction to palliative chemotherapy) (4 mo.), admitted to our department within the same period of time. These cases of smoldering AML (4 women, 2 men) were all of AML2 FAB subtype (4 de novo, 2 post MDS) and presented with a significantly better performance status, lower WBC and circulating blast counts, higher platelet counts and with lower bone marrow infiltration than AML cases with more rapid progression. Cytogenetical analysis when available (3 pts) showed normal karyotypes and clonogenic assay performed in 3 of these patients showed a lack of (2 pts) or reduced in vitro leukemic cell growth (1 pt). The identification of specific characteristics of smoldering leukemia in the elderly might be an important development in the understanding of the physiopathology of acute leukemia and a tool for helping decision-making when selecting the time and intensity of cytotoxic treatment in these older patients.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/32. 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) |
3/32. Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemia.We describe the cases of two patients with philadelphia chromosome-positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL-positive CML.- - - - - - - - - - ranking = 540.09526717785keywords = disease progression, progression (Clic here for more details about this article) |
4/32. 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 = 89.849211196308keywords = disease progression, progression (Clic here for more details about this article) |
5/32. Acquired gain of an x chromosome as the sole abnormality in the blast crisis of chronic neutrophilic leukemia.Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by sustained neutrophilic leukocytosis and absence of the philadelphia chromosome. Most patients with CNL have normal karyotypes, and no specific cytogenetic abnormality has been identified. We report here a patient with CNL that evolved to myeloid blast crisis. A 73-year-old man was admitted to the hospital because of marked leukocytosis (leukocyte count 112.5 x 10(9)/L with 91% segmented neutrophils) and massive hepatosplenomegaly that was diagnosed as CNL with a normal karyotype. After treatment with hydroxyurea for 7 months, the disease progressed to a blast crisis. Bone marrow showed myeloid hyperplasia with 21% myeloblasts, 15% promyelocytes, and marked dysplastic changes of neutrophils. Blastic cells were positive for CD10, CD13, CD14, CD33, CD34, and HLA-DR. Chromosome analysis of the bone marrow cells showed 46,XY, X in all 20 metaphase spreads. We reviewed 15 cases of CNL terminating in the blast crisis and confirmed that all cases transformed into myeloid crises and had poor prognoses. Furthermore, to our knowledge, this is the first case showing the acquired gain of an extra x chromosome as a sole abnormality in CNL. The gain of an extra x chromosome may play an important role in the progression from chronic phase to the blast crisis of CNL.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
6/32. Molecular cytogenetic characterization of a novel additional chromosomal aberration in blast crisis of a Ph-positive chronic myeloid leukemia.We describe a novel chromosomal aberration acquired in blast crisis (BC) in a patient affected by Philadelphia-positive chronic myeloid leukemia (CML). Conventional cytogenetic studies at onset showed a classic t(9;22)(q34;q11.2) in all bone marrow cells, confirmed by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction (b3a2) analysis. In BC, the malignant clone developed a new additional cytogenetic abnormality consisting of a deletion of chromosome 21. To our knowledge, this is the first case of del(21) reported in literature associated with BC CML. The use of an appropriate set of BAC/PAC clones restricted the breakpoint to an interval of approximately 100 kb. sequence analysis did not reveal any known gene in this interval. Oncosuppressor genes distal to the breakpoint could be hypothesized to be involved in the progression of disease toward BC. Identification of new chromosome abnormalities in CML may allow further understanding of specific molecular events leading to disease evolution.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
7/32. 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 = 89.849211196308keywords = disease progression, progression (Clic here for more details about this article) |
8/32. ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis.Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
9/32. Aberrant expression of the LHX4 LIM-homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis.Chromosomal aberrations observed in addition to the philadelphia chromosome in chronic myelogenous leukemia (CML) are likely to be involved in disease progression to the blast crisis. We describe here a t(1;14)(q25;q32) as an additional chromosomal aberration in a patient with CML in biphenotypic blast crisis. By use of long-distance inverse polymerase chain reaction (PCR), we cloned the chromosomal breakpoint and revealed that the immunoglobulin heavy chain gene is fused near its Emu enhancer region to the 5' region of the LHX4 LIM-homeobox gene, whose expression is restricted to the central nervous system. By use of quantitative real-time reverse-transcription PCR, we found that the LHX4 mRNA is expressed at high levels in the patient's leukemic cells and in an acute lymphoblastic leukemia (ALL) cell line. The aberrant expression of the LHX4 gene by the t(1;14)(q25;q32) has very recently been reported in a case of ALL, thus, representing a rare, but recurrent genetic abnormality of possible importance in leukemogenesis.- - - - - - - - - - ranking = 89.849211196308keywords = disease progression, progression (Clic here for more details about this article) |
10/32. Deletion (7)(p11p15) in a patient with Philadelphia-positive chronic myelogenous leukemia.We report a case of chronic myelogenous leukemia (CML) with a Philadelphia (Ph) chromosome. During the transformation phase of the disease, a del(7)(p11p15) and a Ph were identified as additional chromosomal anomalies. We believe that loss of the segment 7p11-->p15 may play an important role in the progression of the disease.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
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