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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS.
Leukemia 1992 Dec
PMID:Measurement of serum cytokine levels in patients with myelodysplastic syndromes. 128 Jul 51

Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.
Leukemia 1992 Mar
PMID:Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. 156 60

Activating ras mutations are frequent (25-60%) in chronic myelomonocytic leukemia (CMML) and in acute myeloid leukemia (AML) (30%), in contrast to chronic myeloid leukemia (CML) in which the incidence is very low (0-3%). This might reflect that the leukemic cell in CML is at a level of differentiation in which ras gene activation is not involved or, alternatively, might be due to the presence in CML of the bcrlabl fused gene. We have analyzed the presence of point mutations in codons 12, 13, 59, 61 and 63 of N-, K-, and H-ras genes, in 26 cases of Philadelphia-chromosome-positive, bcrlabl-positive acute leukemia (Ph+ AL), and in eight CMML cases by using the polymerase chain reaction. Aberrant ras genes were detected in a single Ph+ AL case, and in four out of eight CMML patients. The Ph+ AL showing altered ras allele had an unusual point mutation in H-ras gene, substituting leucine for glutamine. This mutation has not been previously found in any hematological disease. Our findings suggest that ras mutations are probably not involved in the pathogenesis of those leukemias in which blast cells contain bcrlabl oncogene activation.
Leukemia 1992 Apr
PMID:Low frequency of ras oncogene mutations in Philadelphia-positive acute leukemia and report of a novel mutation H61 Leu in a single case. 158 96

Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were seen as isolated, randomly distributed mononuclear cells in normal and regenerating bone marrows. Conversely, QBEND10+ cells were increased and present in aggregates of three or more cells in 6/8 cases of acute leukemia; in two cases of CD34-negative leukemia and in two patients after complete remission no aggregates were seen. QBEND10 immunohistochemistry may therefore be useful for diagnosis and follow-up of myeloid leukemias. In addition, increased numbers of CD34+ cells arranged in clusters were seen in 4/9 cases of refractory anemia with excess blasts (RAEB), 1 case of chronic myelomonocytic leukemia, 3/3 cases of RAEB in transformation, and in 3/7 cases of chronic myelogenous leukemia: in all these cases, CD34 staining of the bone biopsy may have prognostic value. QBEND10+ endothelial cells were significantly increased in all the pathological conditions examined (1.43% of all nucleated cells versus 0.80% in normal bone marrow; p = 0.0063), but especially in myeloid leukemias and in two fibrotic syndromes examined.
Leukemia 1991 Dec
PMID:Identification of CD34+ cells in normal and pathological bone marrow biopsies by QBEND10 monoclonal antibody. 172 30

In an attempt to identify prognostic factors for survival and leukemic transformation, 235 untreated patients with primary myelodysplastic syndromes (MDS) were analyzed in a single center retrospective study. To the well known FAB classification of MDS a supplementary group of patients with pure sideroblastic anemia (PSA) was added, characterized by the absence of dysplastic features of non-erythroid cells. Accordingly, the morphological subtypes were refractory anemia (RA), n = 55; PSA, n = 40; RA with ring sideroblasts (RARS), n = 33; RA with excess of blasts (RAEB), n = 53; RAEB in transformation (RAEB/T) n = 29; and chronic myelomonocytic leukemia (CMML), n = 25. Having screened 28 clinical, cytological, and laboratory parameters by univariate analysis, multiple regression analysis identified six variables with independent prognostic value: percentage of bone marrow blasts, serum LDH activity, PSA, hemoglobin concentration, age, and platelet count. If patients with PSA were excluded, the FAB classification no longer contributed independent prognostic information. Based on the results of this multivariate analysis, a simple scoring system was devised for predicting the survival of patients with MDS. A score of unity was allocated to each of the following parameters: bone marrow blasts greater than or equal to 5%, LDH greater than 200 U/I, hemoglobin less than or equal to 9 g/dl, and platelets less than or equal to 100 x 10(9)/I. As a function of their total score, patients were divided into three risk groups (group A, score 0; group B, score 1-2; group C, score 3-4), which differed significantly in both survival and rates of leukemic transformation. The cumulative survival 2 years after diagnosis was 91% in group A, 52% in group B, and 9% in group C (p less than 0.00005). The actuarial risk of transformation to acute myeloid leukemia at 2 years was 0, 19, and 54%, respectively (p less than 0.05). The inclusion of LDH enzyme levels qualified this scoring system for an accurate assessment of patients with CMML whose prognosis is viewed too favorably when rated by other scores. Furthermore, this score was able to identify those patients with RA and RARS who, without showing an excess of marrow blasts, have an unfavorable prognosis.
Leukemia 1992 Jan
PMID:Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. 173 14

The in vitro culture growth of marrow granulocyte-macrophage progenitors (CFU-GM assay) was studied in 102 consecutive patients with newly diagnosed primary myelodysplastic syndrome (MDS) to determine its diagnostic utility and prognostic value. There were 18 patients with refractory anemia (RA), eight RA with ringed-sideroblast (RARS), 30 RA with excess of blasts (RAEB), 18 chronic myelomonocytic leukemia (CMML), and 28 RAEB in transformation (RAEB-T). Patients with MDS had a significantly lower number of GM colonies and a significantly higher cluster to colony ratio than those of normal controls and patients with cytopenias of other causes. Six in vitro growth patterns were observed; 85% of patients with MDS showed various abnormal growth patterns, and 42% of all MDS patients exhibited a leukemic growth pattern at diagnosis. None of the 40 patients with cytopenias of other causes had a leukemic type growth. A leukemic growth pattern was rarely observed in patients with RA and RARS (4%), but was common in other subgroups (57%). The distribution of various growth patterns was not statistically different among patients with RAEB, CMML, and RAEB-T. Thirty-six patients developed acute leukemia during the follow-up period. The MDS patients with leukemic type growth were at increased risk of rapid progression to acute leukemia, and they also had a shorter survival time than patients with a non-leukemic pattern. These results showed that simply scoring the number of CFU-GM is of limited value for the diagnosis and the prediction of prognosis of MDS, whereas the in vitro marrow culture growth pattern is of prognostic significance independently of the FAB classification. It is concluded that the in vitro growth pattern of marrow CFU-GM is helpful in diagnosing patients with MDS as well as in predicting their clinical outcome.
Leukemia 1991 Dec
PMID:Diagnostic and prognostic values of in vitro culture growth patterns of marrow granulocyte-macrophage progenitors in patients with myelodysplastic syndrome. 177 58

Bryostatin 1 is a macrocyclic lactone which activates protein kinase C (PKC), and is able to induce maturation in cells from some cases of acute myelogenous leukemia. This paper reports that bryostatin inhibits the spontaneous in vitro proliferation of chronic myelomonocytic leukemia cells (CMMoL) in semi-solid medium at concentrations between 10(-8) and 10(-10) M. Growth inhibition was equivalent to or greater than that seen with phorbol-12-myristate-13-acetate. Bryostatin acted primarily as a cytotoxic agent, rather than as a cytostatic agent. The spontaneous in vitro proliferation of CMMoL cells is due to autocrine or paracrine secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). Bryostatin 1 actually increased GM-CSF secretion by CMMoL cells while inhibiting their proliferation. Bryostatin 1 also increased tumor necrosis factor alpha (TNF alpha) secretion by CMMoL cells, and in 2/5 cases the cytotoxic effect of bryostatin 1 on fresh CMMoL cells could be substantially reversed by the addition of antibody to TNF alpha to the culture medium. Bryostatin 1 may produce a cytotoxic effect on CMMoL cells in part by increasing the secretion of, or sensitivity to, TNF alpha, and may have therapeutic potential in CMMoL.
Leukemia 1991 Apr
PMID:Bryostatin 1: a potential anti-leukemic agent for chronic myelomonocytic leukemia. 202 97

Myelodysplasia is an increasingly recognized complication of polycythemia vera (PCV) which often precedes leukemic transformation. This paper describes two patients with aggressive chronic myelomonocytic leukemia, previously undescribed as a complication of PCV. Both patients presented with rapidly increasing splenomegaly which was resistant to treatment with hydroxyurea and external beam irradiation. Splenectomy precipitated fatal hepatic failure in one patient. The other died shortly after transformation to acute myelomonocytic leukemia (FAB M4 classification). Pathology of the bone marrow, spleen, and liver was remarkable for extensive infiltration by dysplastic myeloid elements. Survival was short, only 4-6 months from diagnosis. The unique characteristics in these patients were: (i) prior history of PCV; (ii) rapidly increasing splenomegaly resistant to standard therapy; (iii) absence of overt marrow fibrosis; (iv) hypercellularity (greater than or equal to 90% cellular) of the bone marrow with dysplasia in the myeloid, erythroid, and megakaryocytic cell lines; (v) peripheral monocytosis greater than 1 x 10(9); and (vi) extensive infiltration of the spleen and liver by dysplastic myeloid cells. In addition, the patient who subsequently developed acute leukemia had been treated with hydroxyurea under the PVSG-08 protocol, providing further evidence of the potential leukemogenic effects of this agent.
Leukemia 1991 Jul
PMID:Chronic myelomonocytic leukemia transformation in polycythemia vera. 207 46

Thirty adult patients with CMML were evaluated to determine prognostic factors that might have an impact on conversion to acute leukemia and survival. Neither leukocyte count nor monocyte count correlated with survival. The median survival for all 30 cases was 41 months. Patients with less than 5% marrow blasts had a median survival of 60 months but those with 5-20% blasts had only a 9-month median survival.
Leukemia 1990 Nov
PMID:Chronic myelomonocytic leukemia. 223 90

Members of the RAS gene family have been implicated in many neoplasms with activating mutations around amino acid positions 12 and 61. We have assessed the mutational activation of H, K, and NRAS in myelodysplasia (MDS) by polymerase chain reaction and hybridization with synthetic oligonucleotide probes. Using this method, point mutations in codons 12/13 and 61 of these RAS genes were detected in 20 of 50 patients including two with refractory anemia with ringed sideroblasts (RARS). Ten normal individuals had no detectable RAS mutations. In 11 instances, DNA from patients with detectable RAS mutations were shown to register in either NIH3T3 focus-forming or nude mouse tumorigenicity assays. In addition, one patient (RARS) was shown to have an activated NRAS gene detected by a tumorigenicity assay and Southern blot analyses. Two MDS patients had mutations detected in two different RAS genes. DNA from one of these patients was observed to give rise to transformants with activated N and HRAS. Two patients with detectable NRAS mutations in the MDS stage progressed to AML and DNA from the AML stage registered positively in a transformation assay with NRAS activation. These results show that RAS mutations can occur at early, as well as late, stages of leukemic progression. The incidence of RAS mutations appears to be significantly higher in CMML than in the other subgroups (p = 0.02).
Leukemia 1988 Aug
PMID:RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. 316 76


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