Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and thirty-three cases of myelodysplastic syndromes studied during the last ten years were revised. Of them, 79 were males and 54 females, and their ages ranged between 15 and 91 years (median, 69 years). Five patients (3.7%) had secondary myelodysplasias. The haematological phenotype (FAB) of the cases was: RA, 41.3%; SRA, 24%; RAEB, 18%; RAEBT, 3.7%; CMML, 8.3%. Leucopenia/thrombocytopenia without initial anaemia was present in 4.5% of the cases. Abnormal karyotype was found in 54 patients (40.6%), MIKA in 41 cases and MAKA in 13 cases. The cytogenetic anomalies most commonly found were +8, 5q-, -7, 11q- and 13q-. Cytogenetic abnormalities were commonest amongst the RAEB (50%), and least frequent in CMML (18.2%). Thirty-one patients evolved into acute leukaemia (29 ANLL and 2 ALL). Such blastic changes were more frequent in RAEB (62.5%) and rarest in SRA (9.4%), and they appeared mostly in patients with complex karyotype (MAKA) (53.8%) as compared with those who had normal karyotype (17.7%). Short-lasting complete remission was achieved by 40% of the patients treated with conventional chemotherapy. The survival of the group as a whole (median 30 months) varied in accordance with the haematological phenotype: SRA, 81 months; RA, 65 months; CMML, 13 months; RAEB +/- T, 8 months. The finding of a MAKA karyotype significantly shortened the survival (4 months) with regard to MIKA (44 months) or normal karyotype (39 months). The following median survivals were attained after patients' staging (Bournemouth's criteria): stage A, 84 months; stage B, 22 months, and stage C, 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Myelodysplastic syndromes. Hematologic phenotypes, cytogenetic expression and clinical course in 133 cases (1979-1989)]. 227 38

We report on 37 adults aged 50 years or less with de novo myelodysplastic syndrome (MDS) (excluding cases secondary to chemo or radiotherapy), who represented 6.7% of our total cases of adult MDS. Median age was 42 (range 18-50). At diagnosis, there were 9 RA, 6 RAEB, 13 RAEB-T, 9 CMML but no RARS. Five patients had a familial history of MDS, and 3 a history of occupational exposure to potential carcinogens. Twenty-one patients received intensive chemotherapy (at diagnosis or during the evolution) but only 8 (38%) achieved complete remission (CR), and median CR duration was 10 months. Five patients were allografted (3 of them as first line therapy): 2 remained disease free after 12 and 10 months, and 3 died of transplant related complications. Median actuarial survival of the 37 patients was 21 months. Significantly shorter survival was seen in patients who had circulating blasts, Bournemouth score greater than 1 or 2, abnormal karyotype (especially monosomy 7) and RAEB or CMML. When compared with our MDS aged more than 50, our MDS aged 50 or less were characterized by more familial cases, more cases of RAEB-T and less cases of RAEB and RARS, more frequent abnormal karyotype and monosomy 7, more frequent progression to AML, identical overall survival but longer survival in RAEB-T and shorter survival in CMML. MDS in younger adults seem relatively often familiar or associated to occupational exposure. They have a poor prognosis with conventional therapeutic approaches and therefore require allografting, whenever possible.
 ...
PMID:de novo myelodysplastic syndromes in adults aged 50 or less. A report on 37 cases. 228 Jun 3

A monosomy 7 was first detected in a 6-month-old boy with a chronic myelomonocytic leukemia. After etoposide treatment, relapse occurred after 29 months, with transformation of the disease into an acute myeloblastic leukemia. After bone marrow transplantations, two abnormal clones were found in marrow cells: 45,XY,-7,del(12)(p11p12)(66%), and 45,XY,-7,t(3;12)(q26;p12)(33%). Several karyotypic studies performed until the terminal phase exhibited the persistence of these two clones in the same proportion, although both independently acquired additional and often similar anomalies. The clone with t(3;12) acquired der(7),der(11),der(17),der(8),der(10),-5,-20, and the clone with del(12p), del(5q),der(4),der(8),der(10),der(17),-5,-20. The anomalies in 12p12 appear to represent an important although secondary event of the neoplastic process. The other anomalies may correspond to either those of a secondary acute nonlymphocytic leukemia, since they occurred after treatment by etoposide and alkylating agents, or to the natural evolution of myelomonocytic leukemia.
 ...
PMID:Biclonal chromosome evolution of chronic myelomonocytic leukemia in a child. 229 78

A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or RT for Hodgkin's disease (eight cases), solid tumours (three cases) and multiple myeloma (one case). Clonal chromosome abnormalities were found in bone marrow or peripheral blood cells in all the 12 cases. Five patients had a clonal abnormality of chromosome no. 5 (monosomy, deletions, translocation and inversion of 5q). The critical region on chromosome no. 5 comprised bands q12-q34. Monosomy and deletion of chromosome 7q was observed in the other two patients. In the six remaining patients various karyotypic patterns were observed including a t(4;11) (q21;q23) in one case, monosomies (four cases) and trisomies (one case) of different chromosomes. In the other 15 cases, the presence of a normal karyotype together with the morphological and immunophenotypical characterisation was consistent with a diagnosis of non-neoplastic specimens.
 ...
PMID:Cytogenetic study in therapy-related myelodysplastic syndromes (t-MDS) and acute non-lymphocytic leukaemia (t-ANLL). 232 10

We report on eight patients who were 35 to 77 years old with an isochromosome 17q as the sole structural chromosomal anomaly. Additional numerical chromosomal changes were a trisomy 8 or 17 in two cases each and a trisomy 19 in one case. Five patients had myelodysplastic syndrome (MDS) diagnosed according to the FAB nomenclature as chronic myelomonocytic leukemia (CMML) in two cases, refractory anemia with excess of blasts in transformation (RAEBt) in two cases, and refractory anemia with excess of blasts (RAEB) in one case. One patient suffered from a myeloproliferative disorder (MPS). All cases progressed to acute nonlymphocytic leukemia (ANLL) type M1, M2, or M4 in a period of 2 to 30 months after initial diagnosis, except one patient with RAEBt who died within 2 months. Two patients presented with ANLL-M2 at time of diagnosis. Treatment during the chronic phase of disease consisted of mild cytoreduction and/or substitution of platelets or red blood cells. One patient with CMML received an allogeneic bone marrow graft and relapsed after 33 months with ANLL-M1. Treatment results for overt leukemia were poor, and survival was short, lasting from 1 to 4 months. Overall survival was 1 to 37 months (median duration, 6.5 months). Molecular studies in two cases revealed neither a BCR rearrangement nor a translocation of the ABL protooncogene, as observed in Ph1-positive chronic myeloid leukemia (CML). Thus, an i(17q) anomaly seems to identify a distinct subgroup of mostly myelodysplastic and, less frequently, myeloproliferative disorders that progress rapidly to ANLL, respond poorly to chemotherapy, and are associated with short survival after transformation.
 ...
PMID:Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study. 222 38

The FMS gene encodes the functional cell surface receptor for colony-stimulating factor 1, the macrophage- and monocyte-specific growth factor. Codons 969 and 301 have been identified as potentially involved in promoting the transforming activity of FMS. Mutations at codon 301 are believed to lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. The tyrosine residue at codon 969 has been shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. This study reports on the frequency of point mutations at these codons, in vivo, in human myeloid malignancies and in normal subjects. We studied 110 patients [67 with myelodysplasia (MDS) and 48 with acute myeloblastic leukemia (AML)], 5 patients being studied at the MDS and the later AML stage of the disease. There was a total incidence of 12.7% (14/110) with mutations in codon 969 and 1.8% (2/110) with mutations in codon 301. Two patients had mutations in the AML stage of the disease but not in the preceding MDS and one had a mutation in the MDS stage but not upon transformation of AML. This is consistent with the somatic origin of these mutations. FMS mutations were most prevalent (20%) in chronic myelomonocytic leukemia and AML type M4 (23%), both of which are characterized by monocytic differentiation. One of 51 normal subjects had a constitutional codon 969 mutation, which may represent a marker for predisposition to myeloid malignancy.
 ...
PMID:FMS mutations in myelodysplastic, leukemic, and normal subjects. 240 20

We have developed a RIA for erythrocyte acid glutathione S-transferase (GST), which is immunologically identical to major GSTs from other blood cell components, and measured its serum concentrations in various hematological disorders. In some patients with paroxysmal nocturnal hemoglobinuria, chronic myelomonocytic leukemia, chronic myelocytic leukemia, polycythemia vera and myelofibrosis, the concentrations were high. Very high levels were found in 2 of 3 patients with acute lymphocytic leukemia, while acute myelocytic leukemia exhibited a modest increment. No or little increase was seen in aplastic anemia and myelodysplastic syndrome except chronic myelomonocytic leukemia. It is suggested that the measurement of serum acidic GST may be of use as a clinical marker of increased destruction and/or overproduction of blood cells.
 ...
PMID:Radioimmunoassay for erythrocyte acidic GSH S-transferase. 249 36

Systematic clinical and laboratory observations of 64 cases of myelodysplastic syndrome (MDS) were made. The results showed that malignant clone already exists in the bone marrow of patients with MDS. Eighteen cases of them have transformed into AML. The rates of transforming into AML in RAEB, RAEB-T and CMML were markedly higher than that in RA. The courses of MDS which transformed into AML from the various types were different. The transformation in RA was obviously longer than those in RAEB and RAEB-T. Two cases transformed into myelofibrosis. Diagnosis of CMML according to the FAB classification criteria revealed that it has two forms. One shows only increase of mature monocytes and it has no relation with the types of acute leukemia to be transformed. It is considered as a reactive monocytosis. The other form, in addition to increase of mature monocytes, also has increase of a few monoblasts and promonocytes. These are considered as true CMML and usually quickly developed into M4 or M5 which are related with monocytes.
 ...
PMID:[A clinical study on myelodysplastic syndrome. Report of 64 cases]. 259 Dec 61

A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O). Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated-nuclear megakaryocytes and V, megakaryocytes with bizzare nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V. whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagnosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q-anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS. Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes.
 ...
PMID:[Study on pathophysiology of the myelodysplastic syndromes (MDS)--pattern of dysmegakaryopoiesis related to leukemic transformation]. 259 45

A total of 165 patients were entered into this study and 140 were evaluate for effects and 165 for toxicities. Of 39 patients with chronic myelogenous leukemia (CML) 21 achieved complete remission (CR), 6 achieved partial remission (PR) with a response rate of 69.2%. In MDS, of 11 patients with chronic myelomonocytic leukemia (CMMoL), one good partial response and 4 partial response were observed (CR + PR:45.5%); of 14 patients with RAEB, one complete response, 4 partial response (CR + PR: 35.7%); of 11 patients with RAEB in T, 3 partial response were observed (response rate: 27.3%). Of 13 patients with polycythemia vera, 4 excellent effect and 7 moderate effect (84.6%) were observed. Seven of 30 patients with acute myelocytic leukemia achieved partial response (23.3%). Mean dosages of SM-108 until remission were 400-500 mg/m2/day on CMMoL, RAEB in MDS, polycythemia vera and CML, and 600-800 mg/m2/day on RAEB in T and AML. In the analysis of adverse effects of SM-108, a subjective side effects including mainly gastrointestinal toxicities were observed in 38 cases (23.0%) of the patients : 26 patients (15.8%) showed objective side effects including liver dysfunction, but these symptoms were transient and not serious. Our study indicates that SM-108 is useful agent against MDS, especially CMMoL, RAEB, RAEB in T, polycythemia vera and CML.
 ...
PMID:[Phase II study of SM-108 (4-carbamoylimidazolium-5-olate) in hematological malignancies]. 264 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>