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)

Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.
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PMID:The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. 158 43

Infants with acute leukemia have a poor chance of being cured by conventional chemotherapy. We therefore treated cases of infant leukemia with high dose chemotherapy followed by bone marrow transplantation (BMT). Six suffered from acute leukemia and one from refractory anemia with excess of blasts (RAEB-t). The conditioning regimen consisted of busulfan (BU) and cyclophosphamide (CY), and was intensified by adding etoposide (VP) in four cases. At the time of BMT the children were 4, 5, 12, 13, 13, 14, and 20 months old. Three children were autografted, three received HLA-identical marrow from a sibling donor, and one child received matched unrelated donor marrow. All five children who were grafted in complete (CR) or partial remission (PR) are alive and well in CR 7, 13, 24, 37, and 46 months after allogeneic (two patients) or autologous (three patients) BMT, and 13, 17, 29, 42, and 53 months after initial diagnosis. The child with RAEB-t and the one transplanted in second chemotherapy-resistant relapse of acute non-lymphoblastic leukemia relapsed at 7 and 17 months respectively. The chemotherapy regimen was well tolerated. BU-CY-VP is a promising alternative treatment to regimens including total body irradiation for very young children suffering from acute leukemia.
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PMID:Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation. 161 14

A patient with acute myelomegakaryocytic leukemia (AMMgL), which developed from myelodysplastic syndrome (MDS) after chemotherapy against complicated small cell lung cancer, is reported. The patient was a 66 year-old male, who first presented with moderate macrocytic anemia. Bone marrow aspiration showed absolute erythroid hypoplasia and morphological abnormalities were found in erythroid, granuloid and megakaryocytic lineage cells. Iron utilization studies using radioisotope showed ineffective hematopoiesis. He was diagnosed as having MDS (refractory anemia) and treated with prednisolone, fluoxymesterone, and transfusions. After 3 years, small cell lung cancer was found, but he achieved complete remission with chemotherapy. Since then, pancytopenia progressed with myelofibrosis. Abnormal blasts were found in peripheral blood and gradually increased. He finally died from a blastic crisis resulting in gastric bleeding. The blasts were peroxidase negative, platelet peroxidase positive (10%), and glycoprotein II b/III a antibody positive, indicating megakaryoblasts.
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PMID:[Acute myelomegakaryocytic leukemia developed from myelodysplastic syndrome after chemotherapy against complicated small cell lung cancer]. 164 8

Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used in conjunction with cytogenetic analysis to study the clonality of hematopoiesis in four female patients with myelodysplastic syndromes, treated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and in one patient with essential thrombocythemia (ET) treated with IL-3. Both conventional karyotyping and X-inactivation analysis demonstrated the persistence of a monoclonal pattern of hematopoiesis in the two patients with refractory anemia (RA) treated either with GM-CSF or with IL-3. The partial restoration of non-clonal hematopoiesis was observed in one patient with RA and an excess of blasts following treatment with a combination of GM-CSF and low dose cytosine arabinoside. In a fourth patient with RA and in the patient with ET, treatment with IL-3 resulted in the complete restoration of a non-clonal pattern of peripheral blood cells. In contrast, the bone marrow cells remained monoclonal by Southern blot analysis in the patient with RA in whom it could be tested. Non-clonal lymphocytes appear to have been released into the peripheral blood in the two latter cases and are responsible for the non-clonal RFLP pattern. These results suggest that cytokine therapy may have diverse effects on hematopoiesis, including the release of residual normal cells into the peripheral blood.
Leukemia 1991 Jun
PMID:In vivo effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on clonal and non-clonal cell populations in patients with clonal hematopoietic disorders. 167 79

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

Results of sequential chromosome and cytologic studies in a patient with erythroleukemia (EL) by FAB criteria are described here. Major karyotype aberrations (MAKA) as well as normal karyotypes were detected at presentation, when the patient showed erythroid hyperplasia with moderate leftward shift of erythropoiesis and trilineage myelodysplasia, a picture suggestive of multilineage involvement. Following conventional induction therapy, the patient entered a myelodysplastic phase (MDS) with the features of refractory anemia with excess of blasts and subsequently relapsed with classical EL with maturation arrest of erythroblasts. Chromosome studies revealed a 46, XY karyotype in the MDS phase and only MAKA at leukemia relapse. These findings provide further evidence of a multistep cytogenetic and clinicopathological evolution of EL. Concomitant cytogenetic and morphologic studies in this patient seem to suggest the presence of chromosomally abnormal erythroblasts and confirm the existence of a association between MAKA and maturation arrest of erythroblasts.
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PMID:Clinicopathological evolution and multilineage involvement in erythroleukemia: report of a case. 174 94

We retrospectively evaluated the efficacy of androgen in the treatment of refractory anemia (RA) and compared patient characteristics and the probability of survival in androgen-responder and nonresponder groups. Forty patients with RA were treated in our hospital between 1975-1989, and 27 were treated with various derivatives of androgen. Eleven of the latter responded effectively to androgen therapy, representing an efficacy rate of 40.7%, higher than that of any other treatments thus far reported. The probability of 10-year survival estimated by the Kaplan-Meier method was 75.0% for the responder group and 41.3% for nonresponders, with a median follow-up of 1202 and 1272 days, respectively. In addition, the percent probability of transformation-free survival was higher among androgen-responders than among nonresponders, though the difference was not significant. Transformation from RA to RAEB or overt leukemia was seen in only one case among the former group, but in six among the latter. With respect to patient characteristics, only the percentage of marrow myeloblasts differed significantly between the groups.
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PMID:Androgen in the treatment of refractory anemia. 174 44

An identical extra derivative chromosome resulting from a translocation between the long arm of chromosome 1 and the short arm of chromosome 9, +der(1q9p), has been observed in three patients with a myeloproliferative disorder. Two patients had polycythemia vera in transformation (erythroleukemia in one patient and refractory anemia in the second), whereas the third patient had myelofibrosis which later evolved into acute myelomonocytic leukemia. The two patients who developed overt leukemia did not receive any previous cytotoxic treatment. Non-isotopic in situ hybridization was performed in two patients, allowing for the localization of the breakpoints in 1q12 and 9q12. A similar rearrangement has been previously described in patients with polycythemia vera, either at diagnosis or in advanced stages of the disease. These data suggest that this chromosome abnormality may be consistently associated with myeloproliferative disorders showing a high propensity to transformation, which is not treatment related, and the finding of the +der(1q9p) may represent a poor prognostic sign when observed in the chronic phase.
Leukemia 1991 Dec
PMID:Extra translocation +der(1q9p) is a prognostic indicator in myeloproliferative disorders. 177 54

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

Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA.
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PMID:[Clinical features of atypical refractory anemia (RA)]. 194 25


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