Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the specificity of alkyl-lysophospholipid-induced cell destruction, peripheral blood leukocytes from chronic myelogenous leukemia (CML) patients in chronic phase of the disease as well as in blastic crisis have been separated by density centrifugation. These subpopulations, enriched for the different maturation stages, were tested for their sensitivity to alkyl-lysophospholipids. It is shown that myelocytes in chronic phase CML are resistant, but blast cells from both clinical stages as well as maturational defective myelocytes from blastic crisis CML are highly sensitive to these antimetabolites. In contrast to chronic phase CML myelocytes, these sensitive cells show a high lysophospholipid adsorption rate and lack an O-alkyl-cleavage enzyme.
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PMID:Selective sensitivity of chronic myelogenous leukemia cell populations to alkyl-lysophospholipids. 28 19

The initial rate of phagocytosis, oxygen consumption rate during phagocytosis, bactericidal capacity against Escherichia coli, and the granule protein composition of isolated mature-appearing granulocytes were studied in 23 patients with chronic granulocytic leukemia (CGL) with the simultaneous use of normal controls. The initial rate of phagocytosis was decreased (p less than 0.05) in the CGL patient group, as were oxygen consumption rate (p less than 0.001) and bactericidal capacity (p less than 0.001). Kinetic analysis of the ingestion rate showed CGL granulocytes to have the same capacity to bind the particles as normal granulocytes. Both specific and primary granule protein deficiencies were shown for CGL granulocytes, and these deficiencies were more pronounced at or near blast cell transformation. Analysis of all different granulocyte function parameters showed an inverse correlation to white blood cell counts (p less than 0.01) and to the percentage of immature granulocytes in peripheral blood (p less than 0.001). The leukocytosis doubling time was progressively shortened during the chronic course of the disease. A correlation was found between granulocyte function parameters and leukocytosis doubling time (p less than 0.001), indicating that granulocyte function was progressively deteriorating during chronic phase CGL, and may be an expression of increasing disturbance of the differentiation process.
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PMID:Granulocyte function in chronic granulocytic leukemia. II. Bactericidal capacity, phagocytic rate, oxygen consumption, and granule protein composition in isolated granulocytes. 106 28

To study the regulation of expression of the myc protooncogene, cells from normal individuals and patients with acute myelogenous leukemia (AML), and chronic phase and blastic crisis of chronic myeloid leukemia (CML) cells were put in overnight culture in the presence or absence of fetal calf serum. Myc expression in normal marrow cells and chronic phase CML cells fell after culture in vitro. In contrast, myc expression was maintained or increased in a majority of the AML and blastic crisis CML specimens. These data demonstrate that the regulation of myc expression is disordered in many AML and blastic crisis specimens but not in chronic phase CML cells.
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PMID:Abnormal regulation of the myc gene in myeloid leukemia. 134 25

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.
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PMID:Maintenance of Philadelphia-chromosome-positive progenitors in long-term marrow cultures from patients with advanced chronic myeloid leukemia. 137 77

Marrow cells were exposed to the LNL6 or G1N safety-modified variants of the N2 retrovirus, which contain the G418 bacterial resistance gene neo. The frequency of acquisition of the G418 resistance phenotype following exposure to LNL6 or G1N was compared among hematopoietic progenitor cells from the marrow of patients with chronic phase chronic myelogenous leukemia (CML), blast crisis CML, or from nonleukemic individuals. Under the conditions of our experiments, the myeloid committed progenitor cells from 3 of 6 nonleukemic individuals, 9 of 18 chronic-phase CML patients, and 2 of 4 blast crisis CML patients acquired resistance to at least 1 mg/ml G418 following incubation with cell-free supernatants from the PA317 LNL6 or PA317 G1N producer cell lines. Ten of the 32 colonies growing up in 0.8 mg/ml G418 from chronic-phase marrow exposed to LNL6 were shown to contain the neo gene by polymerase chain reaction (PCR) assay of DNA. These results were consistent with estimates of the transduction frequency based on acquisition of resistance to G418 as the number of colonies growing under G418 selection was always greater at 0.8 mg/ml G418 than at higher concentrations of G418 (1.0-1.4 mg/ml). The average transduction frequency at each G418 concentration (1.0, 1.2, and 1.4 mg/ml) in cells from blast crisis CML cells ranged from 2 to 14%, as measured by acquisition of G418 resistance. Chronic-phase CML showed slightly lower average frequencies of transduction (0.6-2.8% of the colonies are G418 resistant). The average transduction frequency of cells from nonleukemic marrow was as high as that seen from the marrow of chronic-phase CML individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Use of cell-free retroviral vector preparations for transduction of cells from the marrow of chronic phase and blast crisis chronic myelogenous leukemia patients and from normal individuals. 139 Oct 33

The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
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PMID:Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia. 155 89

Suppression or eradication of the Philadelphia (Ph1) chromosome has been a major goal in the therapy of chronic myelogenous leukemia (CML). Variable levels of Ph1 chromosome negativity have been achieved using interferon-alfa, busulfan, combination chemotherapy, and allogeneic bone marrow transplantation. This study evaluated the effect of achieving a predetermined level of myelosuppression using hydroxyurea on bone marrow cytogenetics in CML. Fourteen patients with chronic phase CML received 25 cycles of therapy. Fourteen of the 25 cycles were associated with cytogenetic responses consisting of 25% or more Ph1 negative metaphases (range, 25% to 100%). Nine of the responses consisted of 50% or greater Ph1 negative metaphases. Toxicity was exclusively due to consequences of myelosuppression, including febrile neutropenia and thrombocytopenia. In chronic phase CML, hydroxyurea induces cytogenetic responses with tolerable toxicity and is an attractive agent for further study as a component of treatment strategies aimed at eradicating the Ph1 + population in CML.
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PMID:A phase II pilot trial of high-dose hydroxyurea in chronic myelogenous leukemia. 164 54

The expression of progenitor cell associated antigen CD34 was investigated in cells from 28 patients with chronic myeloid leukemia (CML). The CD34 positivity varied from 0-26% in patients with chronic phases CML (n = 17); from 6-64% in patients with accelerated phase CML (n = 4); and from 27-97% in the patients with blastic crisis of CML (n = 8). The difference in CD34 positivity between chronic (mean 10.1 +/- 2.3%), accelerated (37.7 +/- 13.3%) and blastic (58.0 +/- 7.3%) phases of CML is statistically significant (p less than 0.05), however, the number of patients studied, especially in accelerated and blastic phases is very small. There was no difference in the CD34 positivity of the cells in the peripheral blood and in the bone marrow. CD34 positivity was higher in patients with chronic phase CML at diagnosis (untreated patients) than in those who were studied during treatment. The possible importance of serially studying CD34 positivity in patients with CML is discussed in the paper.
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PMID:Expression of hematopoietic progenitor cell associated antigen CD34 in chronic myeloid leukemia. 171 38

By using antisense oligomers the functional role of the c-abl proto-oncogene in the in vitro growth of bone marrow hematopoietic progenitors from normal subjects and patients with chronic myelogenous leukemia (CML) has been evaluated. Light density bone marrow cells (LDBMs) were depleted of adherent cells, pre-incubated for 15 h with the appropriate oligomer at a concentration of 14 microns, and then plated in methylcellulose for the evaluation of colony formation. Both anti-exon Ia and anti-exon Ib antisense oligomers produced a significant inhibition of normal day 14 CFU-GM growth in vitro (n = 5, 41 +/- 11%, and 36 +/- 7%, respectively; p less than 0.01). In contrast, normal BFU-E growth was not significantly influenced by antisense oligomers (n = 5, 14 +/- 21% and 7 +/- 19%, respectively; p less than 0.05). These findings were confirmed by plating CD34 positive progenitors. When interleukin 3 (IL-3) (100 ng/ml) was added to the culture medium during the preincubation of LDBMCs, the inhibitory effects of antisense oligomers on normal CFU-GM growth were abolished. Seven patients with CML were also studied, all of whom had cytogenetic evidence of 100% clonal hematopoiesis. In five patients in the chronic phase, antisense oligomers were inhibitory on in vitro growth of both day 14 CFU-GM (37 +/- 20% and 37 +/- 15%, p less than 0.05) and BFU-E (45 +/- 15% and 41 +/- 11%, p less than 0.05), and this inhibition was not removed by pre-incubation with IL-3. No significant effect was observed on cluster or colony formation in two patients with CML in accelerated or blastic phase, and on in vitro growth of clonogenic cells from the Ph1-positive K-562 cell line. These findings (i) confirm previous observations showing a lineage specific requirement of c-abl function in normal hematopoiesis, and (ii) suggest that the residual c-abl expression has a role in chronic phase CML hematopoiesis, as its inhibition impairs both myeloid and erythroid colony formation in vitro.
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PMID:c-abl function in normal and chronic myelogenous leukemia hematopoiesis: in vitro studies with antisense oligomers. 173 9

One hundred and sixty-six patients between the ages of 12 and 48 years with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation following single fraction total body irradiation (TBI) of 500 cGy from a cobalt source. Patients also received one of three chemotherapeutic regimens according to their diagnosis or disease status at time of transplant. The median follow-up was 67 months with a range of 33-120 months. The actuarial 5-year event-free survival (EFS) for the subgroup of patients with good risk disease (first complete remission AML and ALL or first chronic phase CML) was 43% with an actuarial relapse rate at 5 years of 26%. Patients with poor risk disease (other than first remission AML and ALL or other than first chronic phase CML) had an EFS at 5 years of 15% with a relapse rate of 62%. Disease status at the time of transplantation was the most important factor predicting outcome in this patient population. We conclude that preparation of good risk patients with chemotherapy and single fraction TBI of 500 cGy at a dose rate of 42-91 cGy/min resulted in EFS and relapse rates similar to those observed by centers using fractionated radiotherapy schedules, without a concomitant increase in toxicity, in particular interstitial pneumonitis and cataracts.
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PMID:Long-term results of bone marrow transplantation for patients with AML, ALL and CML prepared with single dose total body irradiation of 500 cGy delivered with a high dose rate. 179 Apr 25


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