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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognostic value of several clinical and hematologic features, recorded at diagnosis, in chronic phase Ph1 positive chronic myelocytic leukemia (CML), was analyzed in 135 patients using life-table analysis. About one third of patients were atomic bomb survivors and they had been examined twice a year before the diagnosis of CML. In general, features representing tumor cell burden, i.e., leukocyte count, spleen sizes, and absolute differential cell counts of all granulocyte series cells except myeloblasts affected survival significantly, while sex, age, hemoglobin, platelets and features representing quality of leukemia, i.e. neutrophils alkaline phosphatase score, percent Ph1 positive cells in bone marrow, and percent differentials of all granulocyte series cells except promyelocytes and segmented neutrophils were all insignificant. Multivariate life-table analysis was also performed using age, sex, hemoglobin, platelets, and leukocyte count as predictor variables. The result was that leukocyte was the single most important factor in this analysis and annual death rates between low risk (risk ratio less than 0.8) and high risk (risk ratio greater than 1.4) differed considerably up to four years from diagnosis, indicating our formula to calculate risk ratio is valid as a grading parameter of chronic phase Ph1 positive CML within four years from diagnosis.
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PMID:Factors influencing survival in Philadelphia chromosome positive chronic myelocytic leukemia. 695 55

Using postmitotic granulocytes (PMGs) with low neutrophil alkaline phosphatase activity (NAP activity), factor(s) having the capacity to increase their NAP activity were examined in vitro. A high activity of the factor was demonstrated in the cystic fluid of a human squamous cell carcinoma, which is known to produce a large amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). The NAP-stimulating factor increased NAP values both in PMGs from normal bone marrow and PMGs from patients with chronic myeloid leukemia (CML), and NAP values in cells treated with the factor approached or rose above those of normal peripheral granulocytes after 48 hr of culture. The effect of the factor was specific in that the factor caused stimulation only in granulocytic series. These findings may indicate that increases in NAP activity reflect maturation or granulocytes and that low NAP activity of neutrophils derived from patients with CML is due to the immaturity of these cells. The relationship between the factor responsible for the increase in NAP activity and GM-CSF is also discussed.
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PMID:Factor(s) responsible for the increase in alkaline phosphatase activity of postmitotic granulocytes from normal individuals and patients with chronic myeloid leukemia. 697 95

To clarify the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF) in chronic myeloid leukemia (CML), we determined the serum levels of G-CSF in various stages of CML using a very sensitive method: chemiluminescence enzyme immunoassay (CLEIA). This method makes it possible to estimate very low levels of serum G-CSF. In the present study, serum samples from 25 patients in chronic phase and 16 in blastic crisis, as well as samples from 33 healthy volunteers were investigated. The serum G-CSF levels in chronic phase of CML (2.95 +/- 3.91 pg/ml) were significantly lower than those in normal controls (15.92 +/- 6.53 pg/ml) and in blastic crisis of CML (15.52 +/- 17.65 pg/ml) within a range of very low levels (p < 0.001, p < 0.02). Moreover, a reverse correlation between blood neutrophil counts and serum G-CSF levels were clearly demonstrated for CML including blastic crisis (r = 0.405, p < 0.02). Interestingly, a sequential parallel relation was observed between serum G-CSF levels and neutrophil alkaline phosphatase (NAP) scores for a patient with CML in chronic phase. Our observations indicate that a negative feedback mechanism exists between peripheral neutrophils and serum G-CSF levels in the chronic phase of CML, and that very low levels of G-CSF in chronic phase of CML might be an important cause for the low NAP scores.
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PMID:Levels of serum granulocyte colony-stimulating factor in patients with chronic myeloid leukemia. 751 Jan 91

In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes. In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML), in the stable phase of the disease, a weaker interaction between ATRA and G-CSF was documented. The cross-talk between the cytokine and the retinoid was studied in detail in NB4, an immortalized APL leukemia cell line, retaining the 15-17 chromosomal translocation involving the retinoic acid receptor type alpha. The treatment of NB4 cells with G-CSF alone or ATRA alone leads to no increase and to minor induction in LAP activity, respectively. If the cells are treated with the two compounds simultaneously, a dramatic elevation of LAP is observed after 4 days. The synergism between G-CSF and ATRA is evident at concentrations of the retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine between 1 and 10 ng/mL. The simultaneous presence of the two compounds is necessary to obtain maximal increase of LAP activity and the effect is cell density-dependent. Synergism is specific for G-CSF, and it is not observed with other cytokines and functional inducers of the granulocyte. The augmentation of LAP activity is the consequence of an increased transcriptional rate of the liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by Northern blotting and nuclear run-on analysis using specific cDNA probes. Only one of the two possible alternatively spliced forms of L/B/K-type alkaline phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and ATRA. This mRNA form, which is the one observed in normal polymorphonuclear leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G-CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor effects on the expression of these mRNAs.
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PMID:Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells. 751 42

Data of 100 selected CGL patients were considered. There were 50 male and 50 female patients with an average 38.1 and 41.5 years of age, respectively. Seventy nine patients were in stable, chronic and 21 patients were in accelerated phase. Patients first admitted in blastic phase were excluded. Twenty two patients were subjected to bone marrow transplantation. Characteristically low levels of neutrophil alkaline phosphatase were absent in about 10 to 25% of early cases. It was considered that the level of positive cells could eventually point to the extent of normal population. In the group of the accelerated patients the neutrophil alkaline phosphatase scores were regularly high and the serum cholesterol values lower than those among stable-phase patients. The role of G-CSF (granulocyte colony stimulating factor) was considered. Secondary myelofibrosis was frequently associated with low serum cholesterol. Average survival time was 41 month among non-transplanted and 63+ months among identically-transplanted patients. In accordance with the literature, authors point out that in the presence of any factor not permitting transplantation, prolonged high-dose interferon-therapy could be the first choice, because unlike chemotherapeutic agents used till now, it prolongs survival. Apart from this autotransplantation with marrow or with circulating blood derived stem cells should be considered.
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PMID:[Survey of one hundred patients with chronic granulocytic leukemia from the view of recent developments]. 753 45

Juvenile chronic myelogenous leukemia (JCML) is a heterogeneous disorder composed of Philadelphia chromosome-positive (Ph+) CML, which is similar to CML in adults, and Ph-negative (Ph-) CML, a childhood myelodysplasia resembling chronic myelomonocytic leukemia in adults. These two disorders are not always readily separable by leukocyte alkaline phosphatase (LAP) scoring and by karyotyping, yet they have different courses and outcomes. We compared the results of breakpoint cluster region (bcr) gene rearrangement analysis with LAP score and karyotype in these patients. In addition, analysis for immunoglobulin and T-cell receptor gene rearrangement was done to investigate the possibility of mixed myeloid and lymphoid lineage, which has been shown to occur in childhood acute myelogenous leukemia and CML in blast crisis. Peripheral blood and bone marrow samples from six patients with JCML aged 5 to 19 yr were analyzed. One case was Ph+, and five were Ph- by karyotyping. Two samples showed LAP scores of 5 and 11 (one Ph+ and one Ph-); others were normal. All were digested with EcoRI, HindIII, and BamHI for immunoglobulin heavy and light chains and T-cell receptor beta-chain analysis and, in addition, with BglII for bcr analysis. Samples were hybridized with probes to JH, JK, CT beta, and bcr (Oncor). A bcr rearrangement was shown in the Ph+ sample; all others, including one with a very low LAP score, were negative. No JH, JK, or CT beta rearrangements were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Breakpoint cluster region, immunoglobulin, and T-cell receptor gene rearrangement analysis in juvenile chronic myelogenous leukemia. 756 36

The mechanism underlying defective neutrophil alkaline phosphatase (NAP) activity in chronic myelogenous leukemia (CML) was examined using Northern blotting analysis and NAP staining. Fourteen patients with Ph1-positive CML in the chronic phase were included in this study. Polymorphonuclear cells (PMN), containing more than 80% of stab and segmented neutrophils, were collected from peripheral blood (PB) by methylcellulose sedimentation after density gradient centrifugation. Neutrophil alkaline phosphatase mRNA (NAPmRNA) expression was very weak in all patients. When incubated with granulocyte colony-stimulating factor (G-CSF) for 24 h, the PMN of all patients expressed a detectable level of NAPmRNA. NAP score, which semiquantitatively reflects the activity of gene products, was also elevated after incubation with G-CSF in 12 patients. However, a higher dose of G-CSF was required for the maximum response than was the case for normal bone marrow PMN, which also manifested increases of NAPmRNA and its products on stimulation by G-CSF. The present study suggests that the PMN of CML express NAPmRNA and produce its products in response to G-CSF, but that they are less sensitive to G-CSF than normal bone marrow PMN.
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PMID:Induction of neutrophil alkaline phosphatase gene expression by granulocyte colony-stimulating factor in chronic myelogenous leukemia. 768 59

In hematological diseases such as myeloproliferative disorders (MPD) or myelodysplastic syndromes (MDS), some abnormalities in the chemiluminescence of neutrophils are observed. There are two groups; one includes chronic myelogenous leukemia (CML), essential thrombocythemia (ET) and MDS, which all have decreased chemiluminescence of neutrophils. The other group includes polycythemia vera (PV) which has increased neutrophil chemiluminescence. We studied the neutrophil function by analyzing the chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were correlated with those in response to phorbol 12-myristate 13-acetate (PMA). But there were exceptional cases in which the maximal light emission of chemiluminescence (Max CL) in response to FMLP was obviously lower than controls despite the fact that the Max CL in response to PMA was the same as the controls. These facts suggest a heterogenicity of the defect site in these diseases. There was a correlation between the level of chemiluminescence and the neutrophil alkaline phosphatase (NAP) activity in these patients. In vitro culture of CML neutrophils with granulocyte colony-stimulating factor (G-CSF) showed a correlation between the increase in the level of chemiluminescence and NAP activity. These results suggest that NAP may take part in the control of neutrophil function.
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PMID:Chemiluminescence of neutrophils in patients with myeloproliferative or myelodysplastic hematologic diseases--relation to neutrophil alkaline phosphatase activity. 768 68

Early chronic myeloid leukemia (CML) and leukemoid reaction (LR) sometimes show similar histological pictures. In order to assess the efficacy of immunohistochemistry in the discrimination of the two forms, twenty bone marrow (BM) trephines of patient with CML and twenty with LR were immunostained and studied. A wide spectrum of antibodies effective on paraffin-embedded tissues (NP 57 anti-neutrophil elastase, Leu M1, MAC 387, KP1, Y2/51, LCA, UCHL1, L26, BerH2 and Glycophorin A) and directed against granulopoietic, erythropoietic, megakaryocytic, monocytic and lymphoid cells was tested by means of the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Expression of neutrophil elastase in CML and LR showed a different pattern of reactivity in normal and neoplastic granulocytic cells and Y2/51 put in evidence significant discrepancies of megakaryocytes in the two groups. Moreover, a greater number of histiocytic, lymphoid and erythropoietic cells were detected in LR after immunostaining with KP1, LCA, UCHL1, L26 and Glycophorin A. The different immunophenotypical pictures observed, suggest the value of immunohistochemistry as a supplementary diagnostic tool for the differential diagnosis between early CML and LR.
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PMID:[Immunophenotyping of early-phase chronic myeloid leukemia and leukemoid reaction]. 770 38

Treatment of acute promyelocytic leukemia (APL) blasts with cyclic adenosine monophosphate (cAMP) analogs, in combination with all-trans retinoic acid (ATRA), results in the upregulation of the expression of leukocyte alkaline phosphatase (LAP), a marker for the differentiation of the granulocyte. The synergistic interaction between the cyclic nucleotide analogs and the retinoid is not unique to APL cells, as it is observed also in the peripheral granulocytes of chronic myelogenous leukemia (CML) patients. The molecular mechanisms underlying LAP induction were studied in NB4, an immortalized APL cell line. Induction of LAP enzymatic activity is dependent on the time of exposure and on the concentrations of dibutyryl-cAMP or 8-bromo-cAMP and ATRA, two factors that influence the kinetics of appearance of detectable levels of the enzyme. Augmentation of LAP levels by ATRA and cAMP is the result of both transcriptional and early posttranscriptional events and requires de novo protein synthesis. LAP induction correlates with augmentation in the levels of the type I catalytic subunit of cAMP-dependent protein kinase transcript and with granulocytic differentiation. The transcriptional component of the process leading to increased LAP gene expression was reproduced in its main features by transient transfection experiments performed in COS-7 cells using the normal retinoic acid receptor type alpha (RAR-alpha) or the APL-specific aberrant form (PML-RAR) and the upstream promoter of the liver/bone/kidney (L/B/K)-type alkaline phosphatase gene. The promoter is upregulated by treatment with ATRA, and this upregulation is further increased by cAMP analogs.
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PMID:All-trans retinoic acid and cyclic adenosine monophosphate cooperate in the expression of leukocyte alkaline phosphatase in acute promyelocytic leukemia cells. 778 Jan 46


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