A clonal origin of hematopoiesis was studied by investigation of X-chromosome inactivation patterns (XCIP) in isolated granulocyte, CD14(+) and CD3(+) subpopulations obtained from bone marrow and peripheral blood of 36 female patients with primary myelodysplastic syndrome (MDS). Clonality was assessed by PCR amplification of polymorphic short tandem repeats of the human androgen receptor (HUMARA) gene and by investigation of silent polymorphism of iduronate sulphatase (IDS) or p55 genes. On the basis of results in a control group of 20 healthy age related females, a ratio of at least 9:1 between the two alleles was considered a significant marker of monoclonal hematopoiesis. Ten of the 11 patients with advanced forms of MDS (RAEB, RAEB-T, CMML) had clonal granulocytes and CD14(+) cells in peripheral blood. In patients with early disease, only 2 out of 11 patients (18%) with RA or RARS, according to WHO classification, had clonal granulocytes and CD14(+) cells in peripheral blood and bone marrow and 2 other patients with 5q-syndrome exhibited extremely oligoclonal granulocyte subpopulation in bone marrow. In contrast, we found clonal granulocytes in 12 out of 14 patients (86%) with refractory cytopenia with multilineage dysplasia (RCMD) and 8 of them simultanously exhibited clonal CD14(+) cells. Estimated 3 years survival of patients with early disease and clonal cell subpopulations was 61% as compared with 88% in patients without clonal hematopoiesis. Karyotype abnormalities were detected in 11 of the 25 females with early disease. Clonal patterns were present in 7 out of 8 patients with abberations diagnosed by routine cytogenetics, nevertheless, FISH revealed 5q deletion in 3 patients without signs of clonality in XCIP assay. No correlation was found between the presence of clonal subpopulations and the degree of telomere shortening in early MDS. Despite some limitations, the measurement of XCIP remains a sensitive tool for diagnosis of the first transforming mutation in the clonal development of MDS especially when combined with FISH and when an age related group is used to establish an appropriate allele ratio to exclude constitutional or acquired skewing. The occurrence of clonal cell subpopulations in most of the RCMD patients in contrast to RA may reflect a proposed multistep pathogenesis of MDS with dysplastic changes limited to erythropoiesis in early step and with subsequent development of multilineage dysplasia. The results also support the usefulness of separation of RCMD from 'pure' RA; however, a more complex insight combining different molecular techniques performed in a large number of patients is needed for refined classification of MDS on the basis of new molecular prognostic factors and for indication of more effective targeted therapy.

• MeSH
• hybridizace in situ fluorescenční MeSH
• kostní dřeň patologie   MeSH
• lidé MeSH
• myelodysplastické syndromy krev   klasifikace   genetika   patologie   MeSH
• pruhování chromozomů MeSH
• referenční hodnoty MeSH
• refrakterní anemie krev   klasifikace   genetika   patologie   MeSH
• telomery ultrastruktura   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

A retrospective analysis of the relationship between the initial classification according to either FAB or WHO criteria, the presence of risk factors and the type of therapy including stem cell transplantation (SCT) on the survival was performed in a group of 106 patients with primary myelodysplastic syndrome (MDS) of FAB RA subtype. Allogeneic SCT early in the course of the disease did not significantly affect median survival in RA patients evaluated either according to FAB criteria (63.2 months in 17 SCT patients versus 64.4 months in 89 non-transplanted (non-SCT) patients) or in subgroups classified separately according to WHO (64.0 months in SCT versus 91.0 months in non-SCT RA patients and 66.2 months in SCT versus 43.0 months in non-SCT refractory cytopenia with multilineage dysplasia (RCMD) patients) or International Prognostic Scoring System (IPSS) criteria despite decreased incidence of leukemic transformation (5% in SCT versus 32% in non-SCT patients). Neither univariate or multivariate analysis of different clinical and laboratory parameters revealed a significant effect of SCT on 3 or 5 years survival in RA patients. The most probable explanation was a relatively high rate of transplantation related mortality (41%) on one hand together with a slow disease progression towards leukemia (24% at 5 years in non-SCT) on the other hand. A more refined stratification of patients based on the combined WHO morphology classification and IPSS cytogenetic criteria revealed subgroup of 11 non-SCT patients with RCMD and poor karyotype with median survival significantly different from that in five SCT patients (9.2 months in non-SCT versus 89.3 months in SCT, P=0.05). Thus, combined WHO morphology/IPSS cytogenetics criteria may be helpful for identification of the high risk patients with the RA group who may benefit from early SCT despite the relatively high incidence of SCT-related complications.

• MeSH
• cytogenetické vyšetření MeSH
• dítě MeSH
• homologní transplantace MeSH
• kojenec MeSH
• leukemie etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• předškolní dítě MeSH
• prognóza MeSH
• progrese nemoci MeSH
• refrakterní anemie klasifikace   diagnóza   terapie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Světová zdravotnická organizace MeSH
• transplantace kmenových buněk * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

A prognostic impact of WHO classification of myelodysplastic syndrome (MDS) was studied in a group of 103 primary MDS patients with refractory anemia (RA) according to French-American-British (FAB) classification. Median survival of 37 patients with RA according to WHO criteria of 85.2 months was significantly different from that in both 37 patients with refractory cytopenia with multilineage dysplasia (RCMD) (47.0 months, P=0.002) and 29 patients with 5q- abnormality diagnosed by routine chromosome banding (36.2 months, P=0.0002). A more detailed karyotype analysis with fluorescent in situ hybridization (FISH) techniques confirmed 5q deletion as a sole cytogenetic abnormality in only 12 out of 29 patients, in 4 patients 5q- was associated with complex abnormalities involving 5q region, 13 patients had 5q deletion combined with further karyotype abberations outside 5q. No difference in median survival and estimated 3 years survival was observed between RA patients, patients with 5q- syndrome according to WHO morphology criteria and patients with 5q- as a single abnormality confirmed by FISH in contrast to patients with either additional 5q abberations or further karyotype changes not involving 5q. The same difference was also observed in time to 25% of patients evolving to acute myeloid leukemia (AML). Our study confirmed usefulness of separation of RCMD from RA. RCMD represents a poor prognostic subgroup of MDS clearly distinct from pure RA mainly due to short survival connected with progressive bone marrow failure and increased risk of leukemic transformation. We also suggest to define 5q- syndrome as primary MDS of FAB type RA with 5q deletion as a sole cytogenetic abnormality confirmed by FISH analysis. This definition enabled us to discriminate 5q- patients with favorable prognosis similar as in RA from those with poor outcome associated with 5q- combined with complex abnormalities involving either 5q or regions outside 5q.

• MeSH
• analýza přežití MeSH
• buněčný rodokmen MeSH
• chromozomální delece * MeSH
• cytogenetické vyšetření MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• klasifikace metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 5 * MeSH
• mladiství MeSH
• myelodysplastické syndromy klasifikace   genetika   patologie   MeSH
• prognóza MeSH
• refrakterní anemie klasifikace   genetika   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• syndrom MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Aplastic anemia, myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (MPD) are stem cell disorders. There is no clear-cut demarcation of them. Hypoplastic MDS displays features of aplastic anemia and MDS, on the other side mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) develop. In our collection of 566 MDS patients, features of myelodysplasia as well as myeloproliferation, MDS-MPS, were present in 25 patients (4.4%). Twelve patients had at the time of diagnosis megakaryocytic proliferation and thrombocythemia beside signs of MDS, and seven had myelodysplasia with granulocytic proliferation and leukocytosis. In another six patients, MDS was the first diagnosis and the proliferative phase developed later during the course of the disease. These patients can be characterized as MDS-MPS in evolution. All subjects had a variable degree of anemia. While the level of thrombocythemia has been relatively stable, the number of leukocytes has been progressive, but rarely extended beyond 100 x 10(9)/l. Ring-sideroblasts and myelofibrosis were frequent findings. Two more homogeneous MDS-MPS groups emerged in our analysis: sideroblastic anemia with thrombocythemia and a group fulfilling the criteria of Philadelphia chromosome negative and bcr-abl negative "atypical chronic myeloid leukemia (aCML)'. One patient with thrombocythemia and three with leukocytosis (23%) transformed to acute myeloid leukemia (AML). Men prevailed (12/13) in patients with leukocytosis and MDS-MPS in evolution. Of the 46% MDS-MPS patients with chromosomal aberrations, del(20)(q) is of interest.

• MeSH
• chronická myelomonocytární leukemie klasifikace   komplikace   genetika   patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• refrakterní anemie s nadbytkem blastů klasifikace   komplikace   genetika   patologie   MeSH
• refrakterní anemie klasifikace   komplikace   genetika   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sideroblastická anemie klasifikace   komplikace   genetika   patologie   MeSH
• trombocytóza klasifikace   komplikace   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH