Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D03343 (MDS)
 2,225 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Out of 75 consecutive elderly AML patients who did not receive anti-leukemic treatment (52 pts) or failed to respond to differentiating agent (23 pts), 6 patients had survivals of 13.2 to 98 months with treatment restricted to supportive care. This cut-point is far longer than the median survival of the 235 elderly patients (3.5 mo.), either untreated (med. survival: 1 mo.) or treated (with treatment ranging from conventional induction to palliative chemotherapy) (4 mo.), admitted to our department within the same period of time. These cases of smoldering AML (4 women, 2 men) were all of AML2 FAB subtype (4 de novo, 2 post MDS) and presented with a significantly better performance status, lower WBC and circulating blast counts, higher platelet counts and with lower bone marrow infiltration than AML cases with more rapid progression. Cytogenetical analysis when available (3 pts) showed normal karyotypes and clonogenic assay performed in 3 of these patients showed a lack of (2 pts) or reduced in vitro leukemic cell growth (1 pt). The identification of specific characteristics of smoldering leukemia in the elderly might be an important development in the understanding of the physiopathology of acute leukemia and a tool for helping decision-making when selecting the time and intensity of cytotoxic treatment in these older patients.
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PMID:Smoldering acute myelogenous leukemia in the elderly. 1049 80

A rare association of der(1;7)(q10;p10) with de novo acute erythroblastic leukemia (AML-M6) in a 63-year-old male is reported. While this unbalanced 1;7 translocation, der(1;7), has been reported often in therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute myeloid leukemia (t-AML), its associations with de novo AML-FAB-M6 have rarely been reported. Although der(1;7) has been reported as a cytogenetic factor for poor prognosis in t-MDS/AML, our patient showed a good response to chemotherapy and obtained complete remission, although longer observation is required to evaluate the prognosis.
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PMID:Derivative (1;7)(q10;p10) in a patient with de novo acute erythroblastic leukemia (AML-M6). 1056 2

The FAB group has defined myelodysplasia in adults but direct application of this categorization to children has been controversial. Consequently, to outline the natural history of the disease better we have retrospectively analysed case reports and series published in English between 1982 and 1996. This study also included children with juvenile chronic myelomonocytic leukaemia (JCML) and monosomy 7 (Mo7). 340 patients were described in 27 publications. The mean presentation age was 5.91 (SD 5.04) years, and 34.9% were female. Constitutional alterations were described in 68 (20%) where refractory anemia (RA) and RA with excess of blasts (RAEB) predominated and were associated with a significantly longer survival. Among all patients progression to higher forms of MDS was noted in 61 (18%). Cytogenetic anomalies were detected in 59% of 227 children, and in 67 it was to Mo7. Amid those with Mo7, the clinical and laboratory characteristics as well as survival, closely followed their FAB type. Of the treatment options described, survival was significantly higher in those who underwent bone marrow transplant (BMT) (46.9%; P = 0.00021). Among children with JMML (CMML/JCML) not receiving a BMT, time to death was shortest in those best described as JCML (absence of constitutional and karyotypic derangement, thrombocytopenia and elevated Hb F). We conclude that children with constitutional abnormalities survive longer, Mo7 disorders are clinically and morphologically heterogeneous and should not be grouped into a single entity and that CMML and JCML may have biological differences. Finally, BMT remains the treatment of choice for those with primary MDS, as intensive chemotherapy is no better than supportive measures.
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PMID:Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management. 1070 66

Partial tandem duplications of the MLL gene have been associated with trisomy 11 in acute myeloid leukemia (AML) and recently, have also been reported for karyotypically normal AML. In order to test the incidence and prognostic importance of this molecular marker, we have analyzed eight cases of AML with trisomy 11 and 387 unselected consecutive cases with AML for partial duplications of the MLL gene. Patients with normal karyotypes and those with various chromosome aberrations were included. De novo as well as secondary leukemias including all FAB subtypes were analyzed. Performing a one-step RT-PCR with 35 cycles using an exon 9 forward primer and an exon 3 reverse primer partial tandem duplications of the MLL gene were demonstrated in 3/8 (37.5%) patients with trisomy 11. In addition, 13/387 (3.4%) of unselected cases revealed a tandem duplication. Ten of these 13 cases were cytogenetically normal, the other three cases had < or =2 additional chromosomal alterations. Sequencing of the RT-PCR products of all 16 positive cases revealed fusions of MLL exon 9/exon 3 (e9/e3) (six cases), e10/e3 (three cases), e11/e3 (four cases) or combinations of differentially spliced e10/e3 and e11/e3 (three cases) transcripts. The duplications were confirmed by genomic long range PCR and Southern blot hybridization. Twelve cases with the MLL duplication were de novo myeloid leukemia, one was a secondary AML after MDS, three were therapy-related AML (t-AML). Of the 16 MLL-duplication positive cases, seven were classified as FAB M2, two as M1, five as M4, one as M0, one as M5b. The mean age was 62.3 years for patients with MLL duplication vs 50.3 years for the control group. Of 15 adult patients, 12 received treatment. Of these, three were nonresponders, five had early relapse (< or =6 months), four relapsed between 7 and 12 months. Median survival and relapse-free interval of the MLL duplication positive group was significantly worse than those of an age-matched karyotypically normal control group. In conclusion, MLL tandem duplications (1) are less common than previously reported; (2) are preferentially observed in AML with normal karyotypes, but can also be found in the presence of chromosome alterations; (3) are not strongly associated with an FAB subtype; (4) were not observed with the prognostically favorable t(8;21), inv(16), and t(15;17), other recurrent translocations, or in complex karyotypes; and (5) identifies a subgroup of patients with an unfavorable prognosis.
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PMID:Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. 1080 9

We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT. With a median follow-up of 36 months after ASCT, there were no cases of MDS/AML among the 229 patients. In the selected cohort of 60 patients, three (5%) showed clonal chromosomal abnormalities (two single trisomy X and one t(1;6)), whereas two additional patients showed non-clonal reciprocal translocations. Two of the patients with clonal aberrations had blood cytopenias as well as subtle dysplastic pictures in BM which were not classifiable as MDS according to the FAB criteria. Similar dysplastic features were also observed in four patients with normal karyotypes. All cytogenetic aberrations were transient and disappeared, except a +X detected by FISH in a residual cell population in one of the patients. Retrospective cytogenetic and FISH studies of samples obtained after six cycles of FAC/FEC and before transplant demonstrated no chromosomal abnormalities in any of the five patients with post-ASCT karyotypic changes. Early changes in karyotype detected in breast cancer patients following ASCT are transient and do not correlate with or predict development of MDS/AML. As these aberrations were not present before ASCT, they may be related to the HDCT regimen or transplant procedure rather than to the prior adjuvant therapy. Our results suggest that ASCT may be less likely to cause MDS or AML in breast cancer patients as compared to other malignancies. Bone Marrow Transplantation (2000) 25, 1203-1208.
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PMID:Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome. 1084 34

By keeping a cytomorphological basis for the diagnosis of leukemia according to the FAB classification, a new classification system was proposed by the WHO group, which incorporated four genetically established entities of acute leukemia. This classification also made some changes in MDS categories and provided new criteria for diagnosing acute myeloid leukemia. Combined use of this classification with the FAB classification will promote investigations into leukemia.
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PMID:[New classification of leukemia]. 1139 36

The category 'refractory anemia with excess blasts in transformation (RAEBt)' consists of two sub-sets; one group is categorized based on the percentage of blasts in the marrow (> or =20%) and other is based on the percentage of blasts in the peripheral blood (> or =5%). We separated RAEBt patients based on these two criteria and compared hematologic and clinical relevance to assess the reasonable basis for the new classification. All RAEBt patients showing peripheral blood (PB) blasts of > or =5% were re-classified as RAEB by the WHO classification. This subset of RAEBt patients had lower percentages of bone marrow (BM) blasts, and notably they showed frequent complex cytogenetic abnormalities, including -5/5q- and/or -7/7q-. Moreover, the RAEBt patients of this group had shorter survivals compared to RAEBt patients with BM blasts between 20 and 30%. We next assessed hematologic and clinical relevance between refractory anemia with excess blasts (RAEB) and RAEBt patients with PB blasts of > or =5%. Except for the percentage of blasts in the PB (P=0.0037) and BM (P=0.0073), there was no significant difference in hematologic or clinical features between RAEB patients with BM blasts of > or =11% and RAEBt patients with PB blasts of > or =5%. When MDS patients with PB blasts of > or =5% (RAEBt by the FAB classification) were included as RAEB-II based on the "MDS 2000 classification', there was a high frequency of patients with complex chromosome changes, involving 5q and 7q, with significant poorer outcome compared to those with RAEB-I. Although it is still controversial whether MDS patients with BM blasts 20% or more should be considered as acute leukemia, the utilization of the 'MDS 2000 classification' might be useful to designate MDS patients diagnosed based on the percentage of blasts in the peripheral blood.
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PMID:Re-evaluation of refractory anemia with excess blasts in transformation. 1159 28

We investigated the possibility that myeloid cells from the bone marrow (BM) of myelodysplastic patients differ in their expression of CD44 antigen compared with expression of the antigen in normal controls. In addition, two triple-surface marker assays incorporating, respectively, CD44/CD33/CD66 and CD33/CD34/HLA-DR were used to evaluate the degree of myeloid maturation and assess the number of blasts in BM by flow cytometry. Patients with early-stage myelodysplastic syndrome (MDS; RA [FAB classification]) have significantly decreased expression of CD44 on gated myeloid cells. In contrast, patients with late-stage MDS (RAEB and RAEB-T [FAB classification]) showed an elevated expression of CD44 and an increased number of CD34 blasts compared with early-stage MDS patients and normal controls. Late-stage MDS patients also had an increase in the immature myeloid compartment (CD66 weak expression) compared with early-stage MDS patients and normal controls. We have already included this assay as part of our MDS evaluation protocol alongside BM morphology and cytogenetics.
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PMID:Immunophenotypic characterization of myelopoiesis in early and late myelodysplastic syndromes: use of CD44 as an aid in early diagnosis. 1221 Jun 2

We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients' median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.
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PMID:Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. 1259 27

Between 1989 and 1999, 36 cases with primary myelodysplastic syndromes were diagnosed. They were 15 male and 21 females, the median age was 62 years (range: 22 to 90 years). Eighty one per cent of patients were presented symptoms of anemia. Lymphadenopathy, splenomegaly and skin manifestations were noted in 25% of cases. Hemogram showed anemia, leucopenia and thrombocytopenia respectively in 97%, 44% and 55% of cases. Refractory anemia with excess blasts (AREB) is the most frequent FAB subtypes of MDS (17 cases). Cytogenetic study concerned 24 patients. In 13 cases the karyotype was pathological with deletion 5 q in 64% of cases. Seventeen patients have received a chemotherapy. Survival rate to 36 months is 11%. At the time, the only curative treatment is the bone marrow transplantation, which is proposed to young patients with HLA identical donor.
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PMID:[Adult primary myelodysplastic syndromes. Report of 36 cases]. 1284 3


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