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At least 55 records · Page 3Linked to original sources
PubMed1999

Evi-1 and MDS1-Evi-1 genes in pathogenesis of myelodysplastic syndromes and post-MDS acute myeloid leukemia.

OBJECTIVE: To investigate expression of Evi-1 and MDS1-Evi-1 genes in myelodysplastic syndromes (MDS) and post-MDS acute myeloid leukemia (post-MDS AML), and its role in pathogenesis or progression of MDS and post-MDS AML. METHODS: Expression of Evi-1 and MDS1-Evi-1 genes was examined in 31 MDS, 11 post-MDS AML, and 34 de novo AML patients by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Evi-1 expression was not detected in bone marrow samples of 8 normal controls, but low MDS1-Evi-1 expression levels (MDS1-Evi-1/GAPDH < 0.1) were detected in 3 of the 8 controls. Evi-1 RNA was expressed in 1 of 8 RA, 8 of 13 RAEB and 6 of 9 RAEB-T patients, and the percentage of Evi-1 expression in RAEB(T) patients was higher than that in RA (P < 0.05). MDS1-Evi-1 expression was detected in 5 of 8 RA, 9 of 13 RAEB and 5 of 9 RAEB-T patients, and MDS1-Evi-1 expression levels (MDS1-Evi-1/GAPDH > 0.1) were markedly higher than those in the controls. Evi-1 expression was gradually increased in 4 of 5 RAEB-T patients with transformation from MDS to AML. The percentages of Evi-1 and MDS1-Evi-1 expression in post-MDS AML patients were significantly (P < 0.01 and P < 0.05 respectively) higher than those in de novo AML. The colonies of hematopoietic progenitor cells were decreased in Evi-1 and MDS1-Evi-1-positive MDS patients as compared with those in Evi-1 and MDS1-Evi-1-negative patients. CONCLUSION: Abnormal expression of the Evi-1 gene and overexpression of MDS1-Evi-1 gene may play a role in the pathogenesis or progression of MDS and post-MDS AML.

Adult↗
PubMed1998

Long-term administration of G-CSF for aplastic anaemia is closely related to the early evolution of monosomy 7 MDS in adults.

There is an increasing incidence of the evolution of myelodysplastic syndrome (MDS) from aplastic anaemia (AA) with immunosuppressive treatment. In paediatric patients G-CSF is also reported to increase MDS evolution, but this process is not precisely understood in children or in adults. Therefore risk factors of MDS evolution in adults are evaluated here. Of 72 patients, five developed MDS. In 47 patients without cyclosporine (CyA) or antithymocyte globulin (ATG) therapy, only one developed MDS with trisomy 8, 242 months after diagnosis. But of 25 patients treated with either CyA or ATG, four developed monosomy 7 MDS within 3 years. Of these 25 patients, 18 were treated with G-CSF and the four patients (22.2%) who developed MDS were found in this group. The cumulative dose and the duration of G-CSF administration were significantly elevated in patients who developed MDS when compared with those who did not, 822.3 +/- 185.0 v 205.4 +/- 25.5 microg/kg (P<0.05) and 187.5 +/- 52.5 v 72.0 +/- 24.6 d (P<0.002), respectively. However these two values for CyA did not differ significantly. Statistically, treatment with CyA, G-CSF and combined G-CSF and CyA were significantly related to MDS evolution. The administration of G-CSF for more than a year was the most important factor (P=0.00). These results suggested that a close relationship exists between G-CSF and subsequent monosomy 7 MDS from AA in adults who receive immunosuppressive therapy. Long-term administration of G-CSF should be prohibited in order to prevent MDS evolution.

Adolescent↗
PubMed2005

Response assessments in low-risk and high-risk myelodysplastic syndromes (MDS).

The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders that differ with regard to etiology, pathologic and clinical features, treatment, and outcomes. MDS are chronic, progressive diseases that may be broadly categorized into early phase ("low-risk") and late-phase ("high-risk") groups based on prognostic criteria and the differential pathologic and cytogenetic features that drive the MDS phenotype in these disease phases. Consequently, the goals for treatment and management options also differ for low-risk MDS compared with high-risk MDS. Alleviation of disease-related complications, including transfusion requirements, and hematologic improvement are key treatment goals in low-risk MDS. In contrast, altering the natural history of disease, including improvements in overall survival and progression-free survival, are the most important treatment goals in high-risk MDS. To address the heterogeneity of MDS in patient populations enrolled in clinical trials and to resolve problems resulting from variability in the quality and quantity of responses to treatment, the International Working Group has developed standardized response criteria for MDS that are relevant for both low-risk and high-risk categories. The application of the standardized International Working Group response criteria in clinical trials is enabling the comparison of results from various clinical trials in MDS. Furthermore, the International Working Group response criteria provide an important framework for clinical development of new treatments options that may be particularly appropriate for specific MDS subsets.

Clinical Trials as Topic↗
PubMed2005

Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study.

BACKGROUND: The objective of this study was to examine the Minimum Data Set (MDS) and Geriatric Depression Scale (GDS) as measures of depression among nursing home residents. METHODS: The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1) a sum of the MDS Depression items; (2) the MDS Depression Rating Scale; (3) the 15-item GDS; and (4) the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant) across cognitive impairment strata. RESULTS: The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. CONCLUSIONS: The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression.

Aged↗
PubMed1996

Minimum Data Set Plus (MDS+) scores compared with scores from five rating scales.

OBJECTIVE: To compare mandated Minimum Data Set Plus (MDS+) ratings of behavior, function, mood, communication, and cognition to ratings of these domains using analogous research instruments. DESIGN: Cross-sectional correlational study of criterion-related validity. SETTING: Three nursing homes in Rochester, New York. PARTICIPANTS: Fifty-two nursing home residents. MEASUREMENTS: Nursing home staff completed the MDS+ for each subject. Research scales were completed by trained research clinicians, independently of and blinded to the MDS+ results, using the Mini-Mental State Exam (MMSE), Brief Psychiatric Rating Scale (BPRS), Dementia Mood Assessment Scale (DMAS), Psychogeriatric Dependency Rating Scale (PGDRS), and Physical Signs and Symptoms Scale (PSMS). RESULTS: MDS+ measures of functional status, cognitive impairment, and communication were highly correlated with comparable research rating scale scores. Pearson correlation between MDS-functional status and PSMS scores was 0.89, between MDS-dementia and BPRS Factor 3 (representing cognitive dysfunction) and MMSE scores was 0.85 and 0.77, respectively, and between MDS-communication and MMSE and PGDRS Item 6 (assessing communication) scores was 0.74 and 0.62, respectively. Behavior and mood scores did not correlate nearly as well with comparable research scale scores. Pearson correlation between MDS- behavior and PGDRS and BPRS total scores was 0.54 and 0.51, respectively , and between MDS-mood and BPRS Factor 1 (depression) and DMAS 1-17 subtotal (mood disturbance) scores was 0.20 and 0.20, respectively. CONCLUSION: This preliminary study in a small sample shows marked agreement between three of the five MDS+ components analyzed and comparable research rating scales and confirms that behavior and mood are difficult to assess with simple instruments.

Activities of Daily Living↗
PubMed1999

Long-term blood product transfusion support for patients with myelodysplastic syndromes (MDS): cost analysis and complications.

Patients with myelodysplastic syndromes (MDS) frequently become dependent on blood transfusions. We analyzed the total transfusion support required, and its complications and cost, following the diagnosis of MDS (total period = 79.7 patient-years) in 50 patients followed at the Minneapolis VA Medical Center. From diagnosis of MDS to transformation to AML or death (the MDS phase), 41 patients (82%) required transfusions. The median numbers of transfused blood products per patient per year of follow-up in the MDS phase were: packed red blood cells (pRBC), 11.1 (range, 0-91.3) units, random donor platelets (RDP), 6.8 (range, 0-581) units, and single donor apheresis platelet packs (SDP): 0 (range, 0-40) collections. In the AML phase (time from diagnosis of secondary AML to death or last follow-up), median transfusion requirements per patient (n = 5) were 24 (range, 8-88) units pRBC, 94 (range, 24-480) units RDP and 3 (range, 0-19) collections of SDP. Overall, 80% of patients required either special processing or selection of blood products, had reactions to blood products or required premedications (specified/complicated transfusions); 94% of all pRBC and 97% of all platelet transfusions were specified/complicated. The median cost of transfusions per patient was $4048 (range, $0-73210) during the MDS phase and $13210 (range, $5288-59010) during the AML phase. During the MDS phase, the median cost was $4877 (range, $0-67050) per patient-year of follow-up; the major proportion of this cost was for pRBC transfusions. Long-term support with frequent transfusions for MDS usually requires specially selected or processed blood products, and is associated with a high incidence of transfusion reactions. This study provides baseline data on the costs of transfusion support for MDS, and can be used for comparing resource utilization and costs of long-term transfusion support (supportive care) with growth factor therapy or disease-modifying modalities such as allogeneic transplantation.

Blood Transfusion↗
PubMed2005

High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis.

The pathophysiology of the myelodysplastic syndromes (MDS) is incompletely understood. Tumor necrosis factor (TNF)alpha levels are elevated, particularly in early-stage MDS, and apoptosis in marrow cells is upregulated. Observations in other models have shown a role for insulin-like growth factor binding protein 3 (IGFBP-3) in TNFalpha-mediated apoptosis. We observed increased levels of IGFBP-3 in the marrow plasma of patients with MDS (P = 0.005) and hypothesized that altered IGFBP-3 levels contribute to the dysregulation of hemopoiesis in MDS by affecting proliferation and apoptosis. Western analysis of marrow plasma from MDS patients revealed an increase in the ratio of intact vs fragmented IGFBP-3 in early-stage MDS (relative to controls) that decreased with MDS disease progression, suggesting increased proteolysis with more advanced disease. Thus, these results provide evidence for dysregulation of IGFBP-3 in patients with MDS. While the data are complex, they are consistent with a modulatory effect of IGFBP-3 on hemopoiesis in MDS. Conceivably, understanding these mechanisms may allow for the development of novel therapeutic strategies.

Adult↗
PubMed2004

[Biologic changes in MDS-L cell line induced by As2O3 and/or TRAIL].

OBJECTIVE: To investigate the biological changes in myelodysplastic syndromes (MDS) myeloid blast cell line MDS-L after different duration and concentration of As2O3/TRAIL (TNF related apoptosis inducing ligand) treatment. METHODS: MDS-L cells were treated with As2O3 and TRAIL at 9 different concentrations and the treated cells were detected at 24 h, 48 h and 72 h for biologic indexes. The same detections were conducted in untreated MDS-L cells and normal and MDS marrow cells as controls. Apoptosis was assayed by flow cytometry after Annexin V-FITC labelling. Differentiation-induction effect of these drugs on the cells were detected by morphologic examination and CD34(+) proportion analysis after 24 hours treatment and further agar culture for 18 days; P15(ink4b) mRNA expression were detected by RT-PCR and its protein expression by DAB immunocytochemistry, P15(ink4b) DNA methylation by methylation specific PCR (Msp). RESULTS: As2O3/TRAIL treatment promoted MDS-L cells to undergo apoptosis and As2O3 plus TRAIL showed obvious differentiation-induction effect on MDS-L. P15(ink4b) mRNA expression was upregulated in MDS-L cell line after different drug treatment but almost no protein expression increased. Increased P15 expression seemed to be related with DNA demethylation effect of these drugs. CONCLUSIONS: As2O3 or/and TRAIL treatment could promote apoptosis of the clonal cells and induce incomplete cell differentiation. The drugs treatment could also increase P15(ink4b) expression in MDS-L cell line through their demethylation effects.

Antigens, CD34↗
PubMed2006

[Apoptosis of in vitro cultured BMMNC from MDS patients induced by arsenic sulfide].

The aim of this study was to investigate the inhibition effect of arsenic sulfide (As2S2) on the growth of in vitro cultured BMMNC from MDS patients and to explore its possible cellular and molecular mechanisms. The apoptosis of MDS cells induced by As2S2 solution of different concentrations were studied with MTT, flow cytometry, and RT-PCR. The results showed that (1) low concentration of As2S2 (0-0.6 mg/L) had no marked inhibition effect on proliferation of MDS cells; (2) after treatment with 1.5-50 mg/L of As2S2, both low risk MDS cells and high risk MDS cells presented typical features of apoptosis with a dose-dependent manner, the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after As2S2 treatment (P < 0.05); (3) BMMNC from MDS patients had higher apoptosis ratio than that of BMMNC from control. It is concluded that BMMNC excessive apoptosis exists in MDS patients; low concentration of As2S2 (0-0.6 mg/L) shows no inhibition effect on proliferation of MDS cells; high concentration of As2S2 (1.5-50 mg/L) induces apoptosis of MDS cells.

Adult↗
PubMed2000

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere.

Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining. Leukemia (2000) 14, 105-111.

Antineoplastic Agents, Alkylating↗
PubMed2005

Emerging data on IMiDs in the treatment of myelodysplastic syndromes (MDS).

Myelodysplastic syndromes (MDS) encompass a spectrum of clinically diverse hematopoietic stem cell malignancies for which there are few treatment options. These disorders display remarkable heterogeneity in their hematologic and pathologic features, with a wide-ranging natural history. Complex interactions between the affected clone and the bone marrow microenvironment drive the pathogenesis and progression of MDS, resulting in ineffective hematopoiesis, blast accumulation, and a variable predisposition for progression to acute leukemia. For early stage, lower-risk patients with MDS, the mainstay of therapy is supportive care, especially red blood cell transfusions, to alleviate the symptoms of anemia. However, these interventions do not target the underlying pathobiology of disease and have questionable impact on the natural disease course. Dysregulated inflammatory, apoptotic, and angiogenic cytokines play major roles in the pathobiology of MDS and represent attractive therapeutic targets. Lenalidomide is an orally bioavailable analogue of thalidomide with more potent immunomodulatory, antiangiogenic, and antitumor activities than the parent compound and with a better safety profile. In nonclinical studies, the effects of lenalidomide include potentiation of clonogenic response to erythropoietin, activation of integrin-mediated adhesion, cell cycle arrest, sensitization to apoptotic signals, and abrogation of cellular response to receptor-initiated trophic signals. These effects have the potential to impact survival and apoptosis of erythropoietic progenitor cells and their progeny. Data from clinical trials of lenalidomide in MDS have shown erythropoietic- and cytogenetic-remitting activities that frequently result in transfusion independence, particularly in patients with 5q- deletion and lower-risk MDS. Decreases in microvessel density in bone marrow specimens from responding patients provide supportive evidence of an antiangiogenic effect in MDS. Adverse effects, most commonly myelosuppression, are generally manageable with dose reduction and growth factor support. Multicenter phase II and III studies are under way to further assess the erythroid and cytogenetic response rates in distinct subtypes of MDS, including 5q- deletion, and to optimize its clinical application.

Chromosome Aberrations↗
PubMed2005

A comparative review of classification systems in myelodysplastic syndromes (MDS).

Reliable classification and prognostic scoring systems for myelodysplastic syndromes (MDS) are needed to facilitate medically appropriate treatment and management decisions. The French-American-British (FAB) classification scheme for MDS was described in 1982 and has become the reference standard for subsequent MDS classification schemes. The FAB classification system divides MDS into five subgroups, based mainly on morphologic criteria and the percentage of myeloblasts in bone marrow (BM). More recently, the increasing availability of BM cytogenetics, immunologic markers, and molecular genetics has provided important information for staging, prognosis, and treatment of MDS. A World Health Organization panel incorporated this new diagnostic information into a revised classification system that modified the FAB criteria while retaining most of its basic features. The major changes included the creation of additional categories (eg, 5q- syndrome), distinction of unilineage from multilineage dysplasias in the refractory anemias, and subdivision of the heterogeneous refractory anemias with excess blasts into two categories based on BM blast percentage. Additionally, some MDS subtypes were removed or merged with other myeloid disorders into newly created categories. In independent validations, the World Health Organization revisions were shown to provide more-homogeneous subgroups of patients and greater prognostic power compared with the FAB system, although controversies remain. The International Prognostic Scoring System combines blast percentage, karyotype, and number of cytopenias to generate a scoring system that reliably estimates survival and risk of transformation to acute myeloid leukemia for patients with MDS. This universally accepted scoring system is often combined with FAB or World Health Organization morphologic criteria to provide a more complete clinical picture and the most accurate prognostic assessment possible. As more is learned about the pathogenesis of MDS at the molecular level, it is anticipated that these classification and scoring systems will continue to evolve to incorporate the new information.

Bone Marrow↗
PubMed2000

Retrovirus-mediated gene transfer of granulocyte colony-stimulating factor receptor (G-CSFR) cDNA into MDS cells and induction of their differentiation by G-CSF.

Myelodysplastic syndromes (MDS) are clonal disorders in which the proper differentiation of hematopoietic stem cells is impaired. There is no effective treatment for this stem cell disorder at present. In an attempt to find a new strategy that promotes the differentiation of MDS blast cells, we tried retroviral transduction of granulocyte colony-stimulating factor receptor (G-CSFR) into an interleukin-3-dependent MDS cell line, MDS-L, since expression of G-CSFR is known to be essential for the differentiation of myeloid progenitor cells and this expression is impaired in most MDS cells. Ectopic expression of human G-CSFR cDNA in MDS-L cells gave rise to granulocytic differentiation by G-CSF stimulation. G-CSF caused the transformants expressing G-CSFR to display a morphological characteristic of mature granulocytes, upregulated CD11b on the cell surface, and improved NBT reduction activity. These results demonstrate that MDS-L cells ecopically expressing G-CSFR are induced to granulocytic differentiation upon exposure to G-CSF, and shed light on the molecular mechanisms of maturation arrest in MDS cells.

Antigens, CD↗
PubMed1990

Myelodysplastic syndrome (MDS)-associated inhibitory activity on haemopoietic progenitor cells.

We studied MDS-associated inhibitory activity, which inhibited colony formation in vitro of granulocyte-macrophage progenitors (CFU-GM). Macrophages obtained from MDS bone marrow mononuclear cells (BM-MNC) when pretreated with granulocyte-macrophage colony stimulating factor (GM-CSF) suppressed the growth of normal CFU-GM. These macrophages were designated as 'MDS-derived inhibitory macrophages'. Media conditioned by MDS-derived inhibitory macrophages (MDS-CM) also suppressed the growth of normal CFU-GM. In the MDS-CM, high levels of prostaglandin E2 (PGE2) and ferritin were found. However, MDS-CM did not contain detectable levels of tumour necrosis factor (TNF) or gamma-interferon (gamma-IFN). Antiserum against human placental ferritin and/or against PGE2 blocked the haemopoietic inhibitory activity to some extent. These results suggest that inhibitory macrophages may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors including PGE2 and ferritin.

Adult↗
PubMed1992

Myelodysplastic syndrome (MDS)-associated inhibitory activity on haematopoietic progenitor cells: contribution of monocyte-derived lipid containing macrophages (MDLM).

We studied myelodysplastic syndrome-associated inhibitory activity (MDS-IA), which inhibited colony formation in vitro of normal granulocyte-macrophage progenitors (CFU-GM). When adherent marrow cells were incubated with fetal calf serum for 21-24 d, monocyte-derived lipid containing huge macrophages (MDLM) developed. MDLM from MDS marrow (MDS-MDLMs) and their conditioned medium (MDLM-CM) consistently suppressed the growth of normal CFU-GM colony formation. MDS-IA was active on CFU-GM during the S-phase and relatively resistant to heating. Monoclonal antibody against H subunit (acidic) ferritin and polyclonal antibody against placental ferritin neutralized the inhibitory activity of MDS-MDLMs. In addition, cell lysates of MDS-MDLMs reacted to both monoclonal anti-H subunit ferritin and polyclonal anti-placental ferritin in Western blotting analysis, indicating that the inhibitory activity was predominantly acidic isoferritin. On the other hand, MDLMs obtained from normal bone marrow had a CFU-GM enhancing activity. These results suggest that MDS-MDLMs may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors, notably H subunit isoferritin.

Adolescent↗
PubMed1995

Hypocellular myelodysplastic syndromes (MDS): new proposals.

To determine whether hypocellular MDS differs from normo/hypercellular MDS, we attempted to identify hypocellular MDS cases either by correcting the bone marrow (BM) cellularity by age (28 patients) or by using a single arbitrary value of BM cellularity (25 patients) and compared these two groups of hypocellular cases to the normo/hypercellular MDS cases (72 patients). 18 patients were common to both hypocellular groups. Patients with hypocellular MDS in both of these selected groups have similar features with regard to age and sex distribution, peripheral blood and bone marrow parameters, FAB subtypes, karyotypes, leukaemic transformation, and survival. However, the median age of patients in < 30% BM cellularity group was higher than those patients in the age-corrected group (69 years v 62 years). The selection of < 30% cellularity excluded 10 cases in the age group < 70 years but included another seven patients in the age group of > 70 years. However, correction of BM cellularity by age revealed that those included patients (selected for < 30% cellularity) who had normocellular BM by their age. Therefore we recommend the age-correcting grouping to ensure comparable series for comparison, for response to treatment, and survival. Finally, BM cellularity does not appear to be an important factor on prognosis in MDS, because patients with hypocellular MDS in both selected groups have similar prognosis to those with normo/hypercellular MDS patients.

Adult↗
PubMed1997

Differences in cell lineage involvement between MDS-AML and de novo AML studied by fluorescence in situ hybridization in combination with morphology.

We have employed fluorescence in situ hybridization (FISH) in combination with standard morphology (MGG/FISH) to identify the clonal involvement of different bone marrow cell lineages in 20 AML patients (14 MDS-AML, 6 de novo AML). Even though the number of cells belonging to the abnormal clone varied between individual cases, the percentage of clonal blasts was similar in MDS-AML and de novo AML patients. The erythropoietic cells appeared to be part of the abnormal clone in 13 of 14 patients with MDS-AML, but only in 1 of 6 with de novo AML. Similarly, clonal granulocytes were detected in 13 of 14 patients with MDS-AML, compared to 2 of 6 with de novo AML. Lymphocytes consistently displayed normal, diploid karyotype. The results suggest that it is possible to distinguish between MDS-AML and de novo AML by the use of MGG/FISH; in de novo AML the abnormal chromosomal clone is generally confined to the immature myeloid cells, while in MDS-AML mature granulocytes and erythroid cells are of clonal origin. It is, however, not possible to conclude that MDS-AML is a "multipotent" type of leukaemia, since it cannot be ruled out that the chromosomally aberrant erythroid cells and granulocytes represent surviving cells from the original MDS clone.

Adult↗
PubMed1994

[Cytogenetic studies on 334 myelodysplastic syndrome (MDS), aplastic anemia (AA) and other hematological diseases].

In order to distinguish various types of MDS, such as RA/AA, RA/ITP or RA/HA, from AA, ITP or HA, bone marrow (BM) cells were studied by using cytogenetic techniques including R-banding karyotypic analysis and sister chromatid differentiation (SCD) assay in 334 cases of hematological diseases (160 MDS, 54 RA/AA, RA/ITP or RA/HA; 60 AA, 3 other known anemias, 38 PNH and 19 ITP). The results showed: (1) karyotypes and SCD values were both normal in more than 90% of AA, PNH, ITP and other known anemias, but they were both abnormal in about 35.6% of MDS and only 13.0% of RA/AA, RA/ITP or RA/HA. These results indicated that cytogenetic techniques were useful in hematological clinic and that RA/AA, or RA/ITP or RA/HA might be pre-RA or atypic RA. This was supported by the results of following up on some RA/AA, RA/ITP or RA/HA cases, (2) clonal abnormal karyotypes were found in 64.4% of MDS. The recurrent chromosomal alterations were +8, 20q-, -5/5q-, -7/7q-, similar to those reported in literatures. (3) 16 MDS cases were followed up and 15 MDS with SCD negative, but one with SCD positive developed leukemia in our hospital. It is suggested that change from SCD positive to negative was indicative of malignant transformation of BM cells. This was supported by the results of cytogenetic analysis in RA/AA, RA/ITP, RA, RAEB, RAEBT and leukemias. (4) Because more structural chromosome alterations occur in SCD negative than SCD positive MDS, the numerous chromosome alterations (monosomy) might occur in earliest development of MDS into leukemias.

Adolescent↗