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

To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.
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PMID:Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical analysis of 117 cases. 965 32

The BCR/ABL rearrangement, the molecular hallmark of chronic myelogenous leukaemia (CML), is rare in acute myeloid leukaemia (AML), being detected in approximately 1% of cases. In the vast majority of CML cases the breakpoint on chromosome 22 falls in the so-called major breakpoint cluster region of the BCR gene. Only a few cases of CML with breakpoint in the minor or in the micro bcr region have so far been reported. The micro breakpoint position has been associated mainly with a mild form of CML, defined as Philadelphia chromosome-positive chronic neutrophilic leukaemia (Ph-positive CNL). Using reverse transcription-polymerase chain reaction (RT-PCR) we report a patient with an acute myeloid leukaemia phenotype at diagnosis who showed a BCR/ABL rearrangement with a breakpoint located in the micro bcr region (e19a2 junction). Cytogenetic analysis showed a progression of the malignant clone, finally leading to cells with two Ph chromosomes, trisomy 8, isochromosome 17q and deletion of the long arms of chromosome 7. The findings of chromosomal changes point to a possibility of blast crisis of CML with a clinically silent chronic phase. Immunoprecipitation and auto-phosphorylation assay revealed the expression, by the patient's blast cells, of an abnormal P230 BCR/ABL protein, which showed for the first time that this protein was constitutively activated in primary cells from patients. This finding may contribute to the understanding of the role of the BCR/ABL rearrangements in determining different leukaemia phenotypes ranging from acute lymphoid and myeloid leukaemias to mild chronic neutrophilic leukaemias.
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PMID:P230 BCR/ABL protein may be associated with an acute leukaemia phenotype. 988 27

Detection of karyotypic clonal abnormalities are prognostically useful in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS), but cytogenetic methods are not sensitive enough to detect low numbers of residual leukemic cells in patients who have achieved complete remission (CR). Fluorescence in situ hybridization (FISH) and fluorescence activated cell sorting (FACS) were used to investigate the frequency and presence of minimal residual disease (MRD) in AML and MDS patients (n = 28) with monosomy of chromosomes 7, 17 and 18 and trisomy of chromosomes 6, 8, 9 and 10 in CR. MRD was detected in all patients with monosomy 7 (n = 10) and followed by relapse in eight patients after 4.8 +/- 3.1 months. In contrast, persistent leukemic cells occurred in 11/12 patients with trisomy 8, but only three of them relapsed after 7.7 +/- 4.0 months. Cox regression analysis showed that cytogenetic class and levels of clonal cells at CR were related to time to relapse (P = 0.001). The level of MRD identified patients at high and low risk of relapse. High absolute levels of proliferating residual leukemic cells correlated with monosomy 7 and high risk of relapse.
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PMID:Quantitation of minimal residual disease in acute myelogenous leukemia and myelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells. 1021 63

Tetrasomy 8 as a sole anomaly in hematological disorders is relatively rare. To the best of our knowledge, only 19 such cases have been described in the literature to date. Of them, acute myeloid leukemia (AML) in 13 (M1, one; M2, three; M4, one; M5, eight), acute lymphoblastic leukemia(ALL) in one, myelodysplastic syndrome(MDS) in 3, polycythemia vera(PV) and myelofibrosis(MF), one case each. Their median survival was 20 weeks. Here, we report the first case of a 29-year-old man with minimally differentiated AML (AML-M0) displaying a tetrasomy 8 clone. Immunophenotyping showed positivity with CD33, CD34 and intracellular MPO, but all lymphoid markers tested were negative. Conventional cytogenetics of bone marrow cells showed 84.9% of metaphases with tetrasomy 8 in addition to 15.1% with normal diploidy. However, Fluorescence in situ hybridization(FISH) using a centromeric probe specific for chromosome 8 revealed trisomy 8 in 14.2% of interphase nuclei besides tetrasomy 8 in 82.4%. The patient died four weeks after diagnosis without therapy. In conclusion, these findings suggest that tetrasomy 8 is associated with a heterogeneous group of myeloid disorders and heralds a bad prognosis. It may be a consequence of clonal evolution of trisomy 8.
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PMID:Isolated tetrasomy 8 in minimally differentiated acute myeloid leukemia (AML-M0). 1034 86

We analyzed 447 patients with de novo AML using alpha-satellite probes for the chromosomes 7, 8, X, and Y and RT-PCR for t(8;21), t(15;17) and inv(16). In 130/447 patients (29%) chromosomal aberrations were found. Thirty-three patients (7%) had a t(8;21); 11 of these had the additional loss of a sex chromosome (p<0.001) and two a trisomy 8. Twenty-nine patients (6%) had a t(15;17); four of these had a trisomy 8. Sixteen patients (4%) displayed an inv(16); four of these had a trisomy 8. Twenty-two patients (5%) had a sole trisomy 8 and one patient the combination of trisomy 8 and trisomy X. Five patients (1%) displayed the loss of a Y-chromosome as the sole abnormality and two patients had a sole trisomy X. In 22 patients (5%) a monosomy 7 was found, and in none of these patients were additional chromosomal aberrations detected by RT-PCR (p < 0.05). In conclusion, trisomy 8 and the loss of a gonosome are frequently associated with structural chromosomal aberrations with a significant association of -X/Y and t(8;21). The absence of these genomic lesions in AMLs with monosomy 7 suggests that the monosomy 7 has a specific role in the development of these leukemias and their clinical course.
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PMID:Association between structural and numerical chromosomal aberrations in acute myeloblastic leukemia: a study by RT-PCR and FISH in 447 patients with de-novo AML. 1042 28

Bone marrow stroma cells from patients with acute myeloid leukemia (AML) display a variety of functional abnormalities. In order to determine whether this is related to an imbalance in the proportion of different stroma cell types or to integration of leukemic progeny into the regulatory cell network, stroma layers were established in mycophenolic acid-treated long-term marrow cultures from 16 patients with AML and 42 controls and analyzed by means of simultaneous membrane immunofluorescence and interphase cytogenetics. Macrophages were identified by CD14 expression, fibroblasts by staining with the AS02 antibody, and malignant cells by leukemia-specific numerical chromosome aberrations, including monosomy 7 and trisomy 8. Compared with normal controls, there was a slight decrease in the proportion of stroma fibroblasts (52+/-27% versus 77+/-5%) in 10-week-old cultures from patients with AML. Two of five AML patients with trisomy 8 and both patients with monosomy 7 had evidence of leukemic stroma cells. Most malignant cells were CD14+ macrophages (3.8-98.1% of all CD14+ cells), but some were AS02+ (2.8-5.2%). AML stroma layers showed a reduced capacity to support the growth of normal hematopoietic cells in standard two-stage long-term cultures, but this was unrelated to the presence or absence of leukemic stroma elements. In conclusion, AML populations vary with respect to their ability to produce a malignant microenvironment. Functional defects in the hematopoietic microenvironment, however, are not limited to AML patients with cytogenetically abnormal stroma cells, but extend to cases without evidence of malignant stroma cells.
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PMID:Origin of stroma cells in long-term bone marrow cultures from patients with acute myeloid leukemia. 1046 42

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate granulocytes, monocytes, and macrophages. We studied the effect of GM-CSF on (clonal) bone marrow (BM) cells obtained from AML patients after 7 days of culture in vitro: BM samples were obtained from 19 AML patients at diagnosis (DIA), from two patients with persisting disease (PERS), from eight patients in complete remission (CR), and from 12 healthy donors. Flow-cytometric comparison of differentiated, CD 15-positive cells or of CD34-positive blast cells before and after cultivation showed that the proportion of CD15-positive cells was increased in nine of 12 healthy BM samples, in 14 of 19 cases at DIA, in one of three cases during PERS, and in five of six cases in CR of AML. The proportion of CD34-positive cells was increased in one of 12 healthy BM samples, in seven of 19 cases at DIA, in one of two cases during PERS, and in three of seven cases in CR of AML. Southern blot analysis (SBA) performed in six cases during the course of AML, before and after cell culture, showed that clonal DNA increased after GM-CSF treatment in three of five cases studied at DIA, in six of nine cases studied in CR, in the one case studied at PERS, and in the one studied at relapse (REL). In one case of trisomy 8 at DIA a normal karyotype was demonstrated in CR. However, after 7 days of cultivation of the cells in GM-CSF the trisomy 8 was detected in two of 17 metaphases isolated from colony-cells from methylcellulose cultures. Our data show that a 7-day treatment of BM cells with GM-CSF induced a differentiation of healthy and leukemic BM cells in the great majority of cases. An enrichment of CD34-positive cells was not achieved in healthy BM samples. However, in 70% of the cases in CR and in 30% of the cases at DIA of AML, clonal CD34-positive cells were enriched. This means that GM-CSF stimulates ('primes') leukemic cell growth in vitro.
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PMID:GM-CSF stimulates proliferation of clonal leukemic bone marrow cells in acute myeloid leukemia (AML) in vitro. 1055 May 55

Fluorescence in situ hybridization (FISH) is suitable for detecting different types of chromosome aberrations on interphase nuclei even in specimens with no or few chromosome metaphases. However, it is not known why FISH is superior to conventional G-banding analysis. The sensitivity of interphase FISH was compared to that of G-banding analysis in 288 leukemia/lymphoma patients for 10 different types of chromosome aberrations: t(9;22) (M- and m-BCR), t(8;21), 11q23 abnormalities, t(15;17), del(5)/-5, del(13)/-13, +8, -7, and +12. The results revealed that t(15;17) positive cells could not proliferate well in culture, leading to underestimation of abnormality by G-banding. Monosomy 7 in acute myelocytic leukemia (AML) and myelodysplastic syndrome (MDS) as well as trisomy 12 and deletion chromosome 13 in chronic lymphocytic leukemias (CLL) were also severely underestimated by G-banding. On the other hand, no discrepancies were observed in t(8;21), t(9;22), translations involving 11q23, or in trisomy 8. These findings indicate the superiority of interphase FISH over conventional cytogenetics for detecting chromosome abnormalities in small clones, especially for monosomy 7 or (15;17) translocations.
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PMID:Interphase fluorescence in situ hybridization overcomes pitfalls of G-banding analysis with special reference to underestimation of chromosomal aberration rates. 1056 97

We determined the type and frequency of chromosomal aberrations in leukemic cells of 478 children diagnosed with acute myeloid leukemia and enrolled in the Pediatric Oncology Group study 8821. Of the 478 cases, 109 (22.8%) had normal karyotypes. Chromosomal abnormalities of 280 patients (58.6%) were classified into subgroups: 11q23 abnormalities (n = 88, 18.4%), t(8;21) (n = 56, 11.7%), t(15;17) (n = 55, 11.5%), inv(16)/t(16;16) (n = 28, 5.9%), trisomy 8 alone (n = 10, 2.1%), monosomy 7 (n = 9, 1.9%), non-Down-associated trisomy 21 alone (n = 7, 1.5%), and rare recurrent chromosomal translocations (n = 27, 5.6%). The remaining 89 patients (18.6%) had miscellaneous clonal abnormalities. Overall, 84.9% of the children achieved a complete remission; the 4-year event-free survival (EFS) estimate was 33.8% +/- 2.4%. Remission rates were significantly higher (96.4%, P =.011) for patients with t(8;21) and inv(16)/t(16;16) but significantly lower (74.5%, P =.022) for those with t(15;17). The 4-year survival rate for all patients was 43.5% +/- 2.4%; for those with an inv(16)/t(16;16), 75.0% +/- 8.6%; a normal karyotype, 53.8% +/- 4.9%; a t(8;21), 51.6% +/- 7.3%; a t(15;17), 39.8% +/- 6.9%; and an 11q23 abnormality, 32.9% +/- 5.1%. Four-year EFS estimates for patients with inv(16)/t(16;16) (58.2% +/- 10.9%, P =.007), t(8;21) (45.1% +/- 7.7%, P =.014), or normal karyotypes (43.1% +/- 5.0%, P =. 012) were higher than the 4-year EFS estimate for all patients, but EFS estimates for patients with t(15;17) (19.6% +/- 8.0%, P =.033) or 11q23 abnormalities (23.8% +/- 4.8%, P =.0013) were lower. EFS estimates did not differ significantly among 11q23 subgroups. Limited analysis suggested that patients with inv(16) can be salvaged better following relapse than those with t(8;21). Thus, patients with an inv(16)/t(16;16) may have high survival rates when treated with chemotherapy alone.
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PMID:Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. 1057 83

Jumping translocation (JT) is a very rare cytogenetic event, occurring especially in cancer. We describe a case of secondary acute monocytic leukemia (AML5b) with a JT involving the 3q13-3qter segment and leading to a partial trisomy 3. Each clone with JT was associated with trisomy 8 or tetrasomy 8. The literature of JT in AML cases is reviewed: only 13 cases of AML associated with JT have been previously described, seven of which are AML4/5 FAB subtype. Jumping translocation involvement in leukemogenesis is discussed. Leukemia (2000) 14, 119-122.
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PMID:Jumping translocation in acute leukemia of myelomonocytic lineage: a case report and review of the literature. 1063 86


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