Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients with typical Philadelphia chromosome positive chronic granulocytic leukaemia (CGL) developed an accelerated phase of the disease characterized by an increase white blood cell count and marked basophilia in the bone marrow and peripheral blood. Histamine levels were extremely high in both patients. Hyperhistaminaemia was manifested as wheezing, urticaria, diarrhoea, and pruritus in one patient and as peptic ulcer disease and peripheral oedema in both patients. In one case, gastric acid studies revealed a very high basal to stimulated ratio (BAO/MAO). Treatment with the investigational agent metiamide, an H2 receptor histamine antagonist, resulted in marked improvement in symptoms and reduction in gastric acid output. Extreme basophilia in CGL may be associated with hyperhistaminaemia, and manifestations of both the H1 and H2 type may occur.
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PMID:Basophilic chronic granulocytic leukaemia with hyperhistaminaemia. 26 9

Twelve cases of Philadelphia chromosome positive chronic granulocytic leukaemia (CGL) in blast transformation have been investigated using ultrastructural peroxidase detection. In all cases, the leukaemic blasts were negative for myeloperoxidase on the basis of standard cytochemistry. In nine cases a variable proportion of blasts contained peroxidase activity detectable only by electron microscopy, permitting definition of their myeloid nature. By their distinct characteristics and localization, different peroxidase activities were recognized. Thus, several types of blasts were identified: megakaryoblasts (MKB), basophil promyelocytes (BPM), myeloid blasts with small granules containing peroxidase (MyB), and proerythroblasts (ProE). MKB were predominant in two cases and present in four cases, mixed with other myeloid blasts. BPM were abundant in one case and present in seven cases. MyB were identified as a majority in four cases. Three cases remained without any peroxidase. It is concluded that ultrastructural detection of peroxidases is of value for the identification of early myeloid blasts. Their high incidence and the simultaneous presence of several myeloid precursors suggest that during the blast crisis the target cell is frequently a pluripotent myeloid stem cell.
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PMID:Ultrastructural localization of peroxidases in 'undifferentiated' blasts during the blast crisis of chronic granulocytic leukaemia. 29 93

We investigated the marrows of 19 patients with advanced Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in long-term marrow culture (LTMC) to determine the frequency of loss of clonogenic leukemic cells in vitro. Sixteen patients were in first chronic phase at a median of 24 months from diagnosis and had received prior therapy with busulphan and/or hydroxyurea. The effect of interferon therapy on loss of Ph+ clonogenic cells in LTMC was also investigated. Of 16 patients who had not previously received interferon, complete loss of Ph+ progenitors was documented by 4-5 weeks in the LTMCs from two (12.5%). Ph+ progenitors persisted at 4-5 weeks in the LTMC derived from 12 patients. Marrows from nine patients treated with interferon were also established in LTMC. Cultures from four patients did not yield colonies with detectable metaphases at 3-5 weeks, while Ph+ clones were present in the cultures initiated with marrows from five patients. Mean hematopoietic colony yields from the adherent layer at 2-4 weeks, and from the supernatant layer at 1-3 weeks, of cultures derived from interferon-treated patients were significantly lower than in LTMCs of patients not treated with interferon (p less than 0.05). The results indicate that in previously treated patients with late chronic phase CML there is a low frequency of conversion of Ph-negative hematopoiesis in long-term culture. Interferon therapy is associated with impaired progenitor yields in LTMC and does not improve selective loss of Ph+ progenitors.
Leukemia 1992 Jun
PMID:Maintenance of Philadelphia-chromosome-positive progenitors in long-term marrow cultures from patients with advanced chronic myeloid leukemia. 137 77

The biology of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) is the subject of much interest. We present a case of Ph+ ALL with a minor breakpoint cluster (mBCR) rearrangement who subsequently relapsed with Ph+ mBCR+ acute myeloid leukaemia and later with Ph+ mBCR+ acute stem cell leukaemia. This case provides further evidence that Ph+ ALL with a mBCR rearrangement may arise from a pluripotent stem cell with similar potential to that of chronic granulocytic leukaemia to undergo blastic crises with differing lineage characteristics.
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PMID:Philadelphia positive acute leukaemia with minor breakpoint cluster rearrangement may be a stem cell disease. 152 Jun 29

Abnormalities of chromosome 16, including inv(16)(p13q22), del(16)(q22), and t(16;16)(p13;q22), have been reported almost exclusively in association with acute myelomonocytic leukemia and are characteristically accompanied by abnormal eosinophils with dysplastic granules in the bone marrow. We observed an inv(16)(p13q22) in two patients with typical Philadelphia chromosome positive chronic myeloid leukemia (CML). The appearance of the abnormality of chromosome 16 was associated with acceleration of disease or onset of blast crisis and with the appearance in the bone marrow of abnormal eosinophils. In both cases the marrow karyotypes were 46,XY,t(9;22)(q34;q11)/46,XY,inv(16)(p13q22),t(9;22)(q34;q11). In these two patients the temporal association of the acquisition of the inversion 16 and the appearance of monocytoid cells and dysplastic eosinophils in the bone marrow further supports the relationship of this karyotypic abnormality with leukemic monocytoid and eosinophilic evolution. This secondary cytogenetic change appears to be an infrequent manifestation of specific phenotypic disease progression in CML.
Leukemia 1992 May
PMID:Inversion of chromosome 16 and dysplastic eosinophils in accelerated phase of chronic myeloid leukemia. 159 3

A lymphoblastoid cell line (SD-1) has been established by Epstein-Barr virus immortalisation of Philadelphia chromosome positive acute lymphoblastic leukaemia (ALL) cells. Using newly derived anti-bcr monoclonal and anti-abl polyclonal antibodies it was demonstrated that both the original leukaemic cells and the derived cell line expressed the p190 form of the bcr-abl protein found in a proportion of cases of Philadelphia chromosome positive ALL. Interestingly, the leukaemia and the derived cell line each displayed different, clonal patterns of immunoglobulin gene rearrangements providing direct evidence that the t(9;22) translocation which results in the expression of the p190 bcr-abl protein must occur before immunoglobulin heavy chain gene rearrangement. In contrast to the leukaemia, which had multiple chromosome abnormalities in addition to the t(9;22), the cell line had the t(9;22) translocation as its sole abnormality. Although SD-1 cells were demonstrated to express continuously the p190 bcr-abl protein, they were unable to form colonies in soft agar and did not cause tumours in splenectomised nude mice. This cell line therefore represents an appropriate target cell line in which to examine the cooperativity of the p190 bcr-abl protein with other activated oncogene products.
Leukemia 1991 Jan
PMID:Establishment of a lymphoblastoid cell line, SD-1, expressing the p190 bcr-abl chimaeric protein. 184 83

In an ongoing phase-II trial we aimed to predict clinical responsiveness of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML) to recombinant IFN-alpha-2C (rIFN-alpha-2C) by pretesting in vitro. From five normal controls and 14 CML patients in chronic phase, bone marrow samples were taken before treatment and tested for antiproliferative activity by rIFN-alpha-2C, using a microagar culture system for BFU-E, CFU-GM, and CFU-Meg. Light-density nucleated bone marrow cells were stimulated for BFU-E and CFU-Meg colony formation with Alpha medium containing 20% serum obtained from a patient with severe aplastic anaemia. CFU-GM growth was induced with conditioned medium from the cell line GCT. In normal controls BFU-E, CFU-GM and CFU-Meg colony formation was inhibited by rIFN-alpha-2C in a dose-dependent manner. BFU-E proved to be the most sensitive cell lineage (IC50: 65; range: 53-116 U/ml) whereas CFU-GM was about 20 times less sensitive (IC50: 643; range: 480-897 U/ml). The sensitivity of CFU-Meg ranged between these two colony types with 50% growth inhibition at an IFN concentration of 160 (range: 68-246 U/ml). A heterogeneous response to rIFN-alpha-2C in vitro was seen in CML patients. Three of the 14 patients were 'resistant' to rIFN-alpha-2C in vitro with IC50 values for BFU-E, CFU-GM and/or CFU-Meg colony formation greater than 10(4) U/ml. Patients were subsequently treated with a daily dose of rIFN-alpha-2C of 5 x 10(6) U. Four patients achieved a complete and six achieved a partial haematological response. Of the four non-responders three rapidly progressed into blastic crisis. Thus it was seen that treatment failure to interferon was accompanied by IFN-resistance in vitro of BFU-E, CFU-GM and/or CFU-Meg colony formation by bone marrow precursors (p less than 0.01). These results suggest a predictive value of IFN-sensitivity testing in vitro in Ph1 + CML.
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PMID:Recombinant interferon-alpha-2C in chronic myelogenous leukaemia: relationship of sensitivity of committed haematopoietic precursor cells in vitro (BFU-E, CFU-GM, CFU-Meg) and clinical response. 238 74

A 31/2-year-old female presented with thrombocytopenia and anemia. The bone marrow showed marked hemophagocytosis with an increase in macrophages. Over the next 2 months, there was a progressive de-differentiation of this monocytic population with the accumulation of blasts in the blood and bone marrow. The blasts had a normal 46XX karyotype and showed no fusion of the bcr and abl genes associated with Philadelphia chromosome positive leukemia. Intensive chemotherapy produced a transient hypoplastic state during which a bone marrow transplant was performed. The bone marrow after transplant again demonstrated a large population of macrophages. These cells continued to de-differentiate over the ensuing year up until the time of the patient's death. The mononuclear blast cell population was inducible toward monocytic maturation in tissue culture by low doses of ARA-c or daunorubicin. These mononuclear blasts expressed c-myc and c-fos mRNA at high levels, a further marker of their proliferative state and monocytic origin.
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PMID:Juvenile chronic myeloid leukemia: oncogene characterization. 251 62

Twenty-seven patients with Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase were treated with low doses of recombinant interferon (IFN) alpha-2b. Ten patients entered a complete and six a partial haematologic remission with a median duration of 5.8 and 9.1 months respectively. Five minor cytogenetic responses were observed. These results are inferior compared to other studies with higher interferon-doses. Fever was an acute side effect after injection of IFN, limb pains and fatigue occurred protractedly. Haematologic side effects, nonspecific EEG changes, weight loss, and development of pulmonary infiltrates were observed in later periods of the treatment. Eight patients developed neutralizing anti-IFN antibodies after 4.2-20.4 months (median 12.8 months). Anti-IFN antibodies were associated with relapse or refractoriness to IFN treatment: five out of nine patients with rising WBC after initial fall had antibodies, while four did not. Two out of four patients with primary non-response had IFN-antibodies. These results may indicate a serious problem in the long-term treatment of CML with recombinant interferon.
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PMID:Recombinant human interferon (IFN) alpha-2b in chronic myelogenous leukaemia: dose dependency of response and frequency of neutralizing anti-interferon antibodies. 276 3

Leukemic cell DNA from patients with Philadelphia chromosome positive chronic granulocytic leukemia in the United Kingdom, Taiwan, and South Africa and of diverse ethnic origins all have identifiable molecular rearrangements of the breakpoint cluster region on chromosome 22 band q11 when screened with an appropriate DNA probe. This result reinforces the highly conserved nature of the molecular lesion in chronic granulocytic leukemia and its suitability as a diagnostic marker for the disease. Since the assay can be performed by sample referral on relatively small numbers of nondividing frozen or dead cells, it is ideally suited for large scale epidemiological and clinical studies, particularly in developing countries where karyotyping services are not readily available.
Leukemia 1987 Jun
PMID:Molecular lesion in chronic granulocytic leukemia is highly conserved despite ethnic and geographical variation. 282 24


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