Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorescence in situ hybridization (FISH) and the reverse transcription-polymerase chain reaction (RT-PCR) were used to examine a patient presenting with acute myelogenous leukemia (AML) FAB M2, and a complex t(4;9;22)(p14;q34;q11.2). The patient's clinical course was characterized by an aggressive leukemia, resistant to intensive therapy including allogeneic bone marrow transplantation. FISH analysis, using two chromosome painting probes and a BCR/ABL specific probe, confirmed the cytogenetic observation of a 22q11.2-->4p14 and a 4p14-->9q34 exchange, and revealed the presence of a 9q34-->22q11.2, respectively. In addition, RT-PCR demonstrated the presence of a BCR/ABL transcript derived from the major breakpoint cluster region (M-bcr) of the BCR gene. This transcript has been shown to generate an active 210 kDa tyrosine kinase protein more commonly observed in chronic myelogenous leukemia. Because the presentation of AML with this ABL-->BCR fusion product is a rare event, it would seem likely that the additional complex chromosomal rearrangement involving chromosomes 4, 9, and 22 played a role in the aggressive presentation and clinical behavior of this patient's leukemia.
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PMID:Complex chromosome 4, 9, and 22 rearrangement in a patient presenting with AML-FAB M2. 907 96

We assessed the chimerism of CD34+ bone marrow cells before donor leukocyte infusion (DLI) on nine occasions in seven patients with leukemic relapse after allogeneic marrow transplantation. The patients suffered from acute lymphoblastic leukemia (n = 1), acute myeloid leukemia (n = 3), and chronic myeloid leukemia (CML; n = 3). Two patients received a second DLI because of disease progression after the first one. The origin of the CD34+ cells was determined by analyzing variable number of tandem repeats with polymerase chain reaction and, in sex-mismatched cases, by fluorescence in situ hybridization. Before DLI CD34+ cells were exclusively of donor origin in four patients. In another patient 41% of CD34+ cells were derived from the donor. No aplasia occurred in these patients after DLI, whereas in the two patients with exclusively recipient hematopoiesis severe aplasia lasting for 5 and 13 weeks necessitated hematopoietic stem cell support. One patient who had only 5% CD34+ donor cells before DLI recovered without stem cell support after 10 days. Two patients in relapse of CML showed a high percentage of BCR-ABL- CD34+ cells of recipient origin before DLI. These BCR-ABL- cells of recipient type did not prevent severe aplasia which indicates that the assessment of BCR-ABL+ hematopoiesis alone is insufficient for predicting aplasia. Our data indicate that in case of sufficient donor hematopoiesis before DLI no persistent aplasia will occur. Thus, evaluation of donor hematopoiesis allows prediction of aplasia after DLI and makes early therapeutic interventions possible.
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PMID:Donor leukocyte infusion for leukemic relapse after allogeneic marrow transplantation: lack of residual donor hematopoiesis predicts aplasia. 912 13

An important step in the oncogenic transformation of hemopoietic cells and the subsequent development of leukemia is the proliferation of tumor cells in the absence of exogenous growth factors. In most cases of chronic myelocytic leukemia and in some cases of acute myelocytic leukemia and acute lymphocytic leukemia, the bcr-abl oncogene is involved in this process. Although the BCR-Abl oncoprotein demonstrates enhanced tyrosine kinase activity in leukemic cells, the mechanism by which this leads to growth factor independence remains poorly defined. One proposed mechanism is the activation of cytokine signal transduction pathways, possibly by an autocrine loop involving IL-3 and/or granulocyte-macrophage CSF. Examination of several different cell lines expressing BCR-Abl demonstrates that some of these cells have constitutive activation of the JAK/STAT signaling pathway. We have found the constitutive activation of STAT5 in most, but not all, cell lines expressing BCR-Abl. This constitutive activation of STAT5 is variably associated with a corresponding activation of JAK kinases. Ab blocking studies show that the activation of STAT5 in these cell lines cannot be attributed to the activation of an IL-3/granulocyte-macrophage CSF-driven autocrine loop. Interestingly, samples of peripheral blood cells derived from patients with acute myelocytic leukemia and chronic myelocytic leukemia, which express BCR-Abl, demonstrate constitutive activation of STAT family members. These studies suggest that in a variety of leukemic states, BCR-Abl may use a bypass mechanism to activate cytokine signal transduction pathways.
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PMID:Constitutive activation of JAKs and STATs in BCR-Abl-expressing cell lines and peripheral blood cells derived from leukemic patients. 936 95

Philadelphia (Ph) chromosome-positive leukemias, with the bcr-abl gene translocation, have a dismal prognosis. The identification of Ph-positive patients is vitally important because only aggressive therapeutic approaches, such as allogeneic bone marrow transplantation, may result in long-term disease-free survival. Routine diagnostic methods, such as Southern blot analysis and cytogenetics, may lead to false-negative results. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis is considered the most sensitive tool for the detection of the bcr-abl translocation, and it is widely used alone or in combination with karyotyping or Southern blot analysis to identify Ph-positive cases. In this study, we used fluorescence in situ hybridization (FISH) with BCR and ABL double-color probes for detecting Ph-positive leukemias. The FISH results were compared with the results of cytogenetic and RT-PCR analyses in 75 patients with leukemia or other myeloproliferative syndromes (chronic myeloid leukemia, 30; acute lymphoblastic leukemia, 24; acute myelogenous leukemia, 6; essential (hemorrhagic) thrombocythemia, 12; chronic myelomonocytic leukemia, 2; and polycythemia vera, 1). FISH analysis proved to be simple, extremely reliable and sensitive; bcr-abl fusion detection was successful in the presence of all types of molecular junctions i.e., (b2a2, b3a2, and e1a2). Furthermore, a Ph-positive case that proved fusion negative by RT-PCR was identified as positive by FISH. The sensitivity of RT-PCR and FISH related to Ph-positive cases were 97% and 100%, respectively. Regarding specificity, in 4 (5%) of 75 patients, RT-PCR provided false-positive results. Cross-contamination was identified because a new specimen was harvested and reanalyzed when FISH, cytogenetics, and RT-PCR results were contradictory. We believe FISH is an optimal diagnostic method to detect bcr-abl translocation that can be used alone or to validate the results of RT-PCR analysis.
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PMID:A comparative analysis of FISH, RT-PCR, and cytogenetics for the diagnosis of bcr-abl-positive leukemias. 942 14

There is strong clinical and epidemiological evidence that ionizing radiation can cause leukemia by inducing DNA damage. This crucial initiation event is believed to be the result of random DNA breakage and misrepair, whereas the subsequent steps, promotion and progression, must rely on mechanisms of selective pressure to provide the expanding leukemic population with its proliferative/renewal advantage. To investigate the susceptibility of human cells to external agents at the genetic recombination stage of leukemogenesis, we subjected two hematopoietic cell lines, KG1 and HL60, to high doses of gamma-irradiation. The irradiation induced the formation of fusion genes characteristic of leukemia in both cell lines, but at a much higher frequency in KG1 than in HL60. In KG1 cells, the AML1-ETO hybrid gene [associated with the t(8;21) translocation of acute myeloid leukemia] occurred significantly more often than the BCR-ABL [associated with t(9;22) chronic myeloid leukemia] or the DEK-CAN [associated with t(6;9) acute myeloid leukemia] fusion genes. These findings support the notion that ionizing radiation can directly generate leukemia-specific fusion genes but emphasize the differing susceptibility of different cell populations and the differing frequency with which the various fusion genes are formed. The selectivity observed at the primary level of gene fusion formation may explain at least in part the differential risk for development of some but not other forms of leukemia after high-dose radiation exposure.
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PMID:Selective induction of leukemia-associated fusion genes by high-dose ionizing radiation. 945 83

A patient with the M2 subtype of AML who had a 45,X,-X,t(8;21) karyotype at diagnosis was found to have the Ph chromosome in one out of 37 evaluated cells 18 months after the initial diagnosis. Interphase FISH studies utilizing a BCR-ABL dual-color probe did not detect a fusion product 4 months prior to the appearance of one Ph-positive cell. Nineteen months post diagnosis and 5 months after clinical relapse all evaluated cells had the Ph chromosome in a clone characterized by t(8;21). These observations suggest that late appearing Ph is a secondary event which may be either therapy-related or consistent with one of the later events in a multistep pathogenesis of AML.
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PMID:Acquisition of the Ph chromosome and BCR-ABL fusion product in AML-M2 and t(8;21) leukemia: cytogenetic and FISH evidence for a late event. 955 10

We describe a patient with leukocytosis with all the stages of neutrophilic series, peripheral dominant myeloblast proliferation, marked dysplasia of myeloid and erythroid series, and extramedullary hematopoiesis of the lymph nodes. A cytogenetic study of the bone marrow cells showed normal karyotype, and molecular analysis of the leukemic cells showed negative for BCR-ABL by RT-PCR. After chemotherapy, the patient went into complete remission with a normal blood and bone marrow profile with no dysplasia. On relapse, the hematological findings showed a typical bone marrow dominant acute myeloid leukemia, with the leukemic cells having a chromosomal abnormality. The patient exhibited the combined features of myeloproliferative disorder, myelodysplastic syndrome, peripheral dominant myeloblast proliferation (so-called peripheral leukemia) and typical acute myeloid leukemia throughout the clinical course. This is thought to be a rare overlapping disease involving these distinct hematological conditions that do not usually occur in the same patient.
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PMID:A rare atypical myeloproliferative-disorder-like hemopathy with marked dysplasia, peripheral dominant myeloblast proliferation and extramedullary hematopoiesis was converted into typical acute myeloid leukemia with an interval of complete hematological remission. 969 15

Fluorescent in situ hybridization (FISH) is a rapid, sensitive and reliable method for the identification of complete chromosomes, or segments of them, during metaphase or nuclear interphase. The present study shows the results of the analysis of 32 bone marrow aspirates from patients with malignant hematological diseases (11 AML, 7 ALL, 12 CML and 2 CLL), referred to the Medical Genetics Unit of the Faculty of Medicine, Zulia University, Maracaibo, Venezuela between 1994 and 1996. All samples were studied by conventional and molecular techniques (FISH), using probes of total chromosomes, alpha-satellites and locus specific. In patients with AML and ALL and FISH technique detected clonal chromosomal abnormalities, that were not found by the conventional cytogenetic technique. Furthermore, the PML-alpha RARA complex was identified in the promyelocytic acute leukemias. The presence of the molecular complex ABL-BCR was also demonstrated in CML. The present study demonstrates the usefulness of the FISH technique in the detection of clonal chromosomal abnormalities, which are important when considering the clinical care of patients with these pathologies.
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PMID:[Clonal chromosome abnormalities in malignant hematological diseases using fluorescence in situ hybridization]. 970 20

We investigated parental origin of rearranged chromosomes 9 and 22 (9q + and 22q -) in five patients with Ph-positive chronic myeloid leukemia (CML) using the C-banding and silver-staining methods of nucleolus organizer regions, respectively; of rearranged chromosome 21 (21q +) in seven patients with t(8;21)-positive acute myeloid leukemia (AML); and of rearranged chromosome 15 (15q +) in six patients with t(15;17)-positive AML. It was found that these rearranged chromosomes can be of either paternal or maternal origin. Although the number of patients examined was small, these results indicate that the genes rearranged as a result of these chromosome translocations (ABL, BCR, AML-1 and PML) are not genomically imprinted.
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PMID:No parental origin bias for the rearranged chromosomes in myeloid leukemias associated with t(9;22), t(8;21) and t(15;17). 971 10

A 46-year-old female presented with acute myeloid leukemia during complete remission of multiple myeloma after extensive treatment with alkylating agents. Leukemic blasts expressed CD34, platelet esterase and gp IIIa. RT-PCR analyses of peripheral blood cells detected a p190 type BCR-ABL rearrangement and high levels of MDR1. The patient expired during neutropenia shortly after induction chemotherapy. Autopsy revealed persistent blasts in the bone marrow, spleen and liver. 'Secondary' acute myeloid leukemia with megakaryoblastic features and p190-type BCR-ABL rearrangement has not previously been reported. The possibility that the combination of a BCR-ABL rearrangement with overexpression of MDR1 may have contributed to the treatment-refractory course is discussed.
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PMID:Drug resistance of secondary acute myeloid leukemia with megakaryoblastic features and p190 BCR-ABL rearrangement. 978 5


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