Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.     

Bone marrow biopsy in myelodysplastic syndromes: morphological characteristics and contribution to the study of prognostic factors

Ten characteristics of bone marrow (BM) biopsies in paraffin sections, obtained at diagnosis from patients with myelodysplastic syndromes (MDS) classified according to the FAB criteria, were analysed to identify both the most relevant morphologic data and any possible influence on survival. Agreement between two observers was obtained for 94% of the data. BM cellularity was increased in 63% of the cases and was higher in refractory anaemia with excess of blasts (RAEB). RAEB in transformation (RAEB-t) and chronic myelomonocytic leukaemia (CMML) (P = 0.001). Dysmegakaryopoiesis and dyserythropoiesis were present respectively in 83% and 72% of the cases, with slight differences among the FAB subtypes. Abnormal localization of immature precursors (ALIP) was found in more than half of the cases and somewhat more frequently seen in the RAEB + RAEB-t + CMML group (P = 0.07). Eosinophilia, plasmacytosis and reticulin fibrosis were evident in 26%, 18% and 47% of the cases respectively. Cellularity (P = 0.006), eosinophilia (P = 0.009) and, to some extent, dysmegakaryopoiesis (P = 0.07) bore a certain relationship with survival on univariate analysis. The presence of ALIP was not seen to affect the outcome. Multivariate analysis showed that the cellularity and presence of dysmegakaryopoiesis, in BM biopsy, added significant independent prognostic information to that achieved with age, platelet count and proportion of blast cells in BM aspirate, three variables with proven prognostic value in MDS patients. Using a regression model including these five characteristics we have stratified the patients into low, intermediate and high-risk groups with different survivals (P = 0.00001). The present findings show that BM biopsy is able to provide both morphological characteristics and information about the prognosis of survival, and should thus be included in the initial evaluation of MDS.     

Prognostic factors in the myelodysplastic syndromes: importance of initial data on peripheral blood counts, bone marrow cytology, trephine biopsy and chromosomal analysis

An analysis of clinical, haematological, histological and cytogenetic data was performed in 85 consecutive patients with myelodysplastic syndromes (MDS). The criteria for diagnosis of refractory anaemia (RA), acquired idiopathic sideroblastic anaemia (AISA) and chronic myelomonocytic leukaemia (CMML) were clearly defined, since the inclusion criteria provided by the FAB co-operative group are imprecise. None of these patients has received chemotherapy during the follow-up period. The median survival of the whole group was only 15 months, with less than 10% of the patients surviving after 5 years. Fifteen patients (17.6%) were still alive at time of analysis, 31 (36.5%) have developed acute myeloid leukaemia (AML) and only one of them is still alive; 30 (35.3%) died of infectious and/or haemorrhagic complications. Patients who developed AML had a shorter survival (median survival time 9.5 versus 15 months) but this difference was not significant (P = 0.10). Factors with prognostic value are in order of significance: abnormal localized immature myeloid precursors (= ALIP) in the trephine biopsy, circulating myeloblasts, excess of blasts in the bone marrow smears, age, FAB classification and granulocyte count. In comparison to refractory anaemia with excess of blasts (RAEB), CMML and RAEB in transformation (RAEBt), patients with RA and AISA had a lower incidence of evolution to AML (11% versus 56%), but a higher mortality rate from infections and/or bleeding (59.2% versus 29%). ALIP negative cases were only found among patients with RA and AISA, whereas ALIP positivity was observed in all cases of RAEB and RAEBt, in 10/11 patients with CMML and in almost half the cases of RA and AISA. In RA and AISA patients survival was significantly different between ALIP positive and ALIP negative cases (P = 0.009). Among MDS patients, ALIP negative cases developed significantly less AML than ALIP positive cases (5% versus 44%), but a similar percentage of mortality from infectious and/or haemorrhagic complications was seen in both groups (33% versus 36.5%). Chromosomal analysis proved to be of no significant prognostic value, although a trend for shorter survival was observed in patients with complex karyotype anomalies or without mitoses. Because of their prolonged survival, antileukaemic chemotherapy is contra-indicated in ALIP negative patients (median survival 50 months). Nevertheless they only constitute a minor subgroup of MDS cases. Prognosis in ALIP positive patients is poor (median survival 12.5 months); in these patients therapeutic trials with cytostatic drugs or with inducers of differentiation of myeloid precursor cells seem to be justified.     

Primary myelodysplastic syndromes: diagnostic and prognostic significance of immunohistochemical assessment of bone marrow biopsies.

Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French-American-British [FAB] types: refractory anemia [RA] = 21; RA with ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB criteria were not applicable) was analyzed for bone marrow histologic and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and reticulin stains were used for morphologic assessment. To identify the cell lineage precisely, chloroacetate esterase staining and an indirect immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin-fixed paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment permitted accurate identification of dysplastic features such as mononuclear and binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone marrow histologic and immunohistochemical features observed were heterogeneity of immunohistochemical staining in various cell lineages, megakaryocytic emperipolesis, alteration of bone marrow microarchitecture, intravascular clusters of hematopoietic cells, and the types of benign lymphoid aggregates. The nature of abnormally localized immature precursors (ALIP) was discerned. Three types of clusters of immature cells were found that were difficult to distinguish on Giemsa and H&E morphology, these were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic and monocytic aggregates (n = 32). The bone marrow histologic and immunohistologic patterns permitted the identification of four groups of clinical relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases in group 2 showing the worst prognosis with early death due to increased propensity to leukemic transformation and cytopenia-related complications (P less than .0001). We conclude that immunohistochemistry is feasible on routinely processed BMB and the information obtained is of diagnostic and prognostic importance in P-MDS. The phenotype of ALIP varies with the morphologic and histologic subtypes of MDS and the term should be reserved for cases in whom the clusters in the intertrabecular region are of myeloid (granulocytic and monocytic) lineage on immunohistochemistry.     

Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes

Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-alpha (TNF-alpha), tumor growth factor-alpha (TGF-alpha), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-alpha, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-alpha levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-alpha in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.     

Myelodysplastic syndromes: a multiparametric study of prognostic factors and a proposed scoring system

In 72 consecutive patients with previously untreated myelodysplastic syndromes (MDS) having a median follow-up of 44.9 (range: 6-198) months, a multiple regression analysis was conducted of the prognosis significance of 26 clinical and laboratory parameters, including bone marrow (BM) biopsy characteristics. Parameters which had independent prognostic meaning served to construct a scoring system for survival prediction. Only 7 parameters were significant: hemoglobin, BM cellularity, BM blast percentage, abnormal location of immature precursors (ALIP), fibrosis, dysmegakaryopoiesis and the erythro/myeloid ratio. They enabled us to predict 42% of all MDS patient survival (p less than 0.03) and 84% (p less than 0.02) of survival of patients who lived over 20 months. Based on the value of these parameters in individual cases, the patient population had a score ranging from 0 to 13, with a median value of 5. Median survival of patients with a score less than or equal to 5 was 117, while that of patients with a score greater than 6 was 33 mos. This scoring system, which has been draw from a wide panel of clinical and laboratory parameters, will be verified on prospective studies.     

The incidence and outcome of myeloid malignancies in 2,112 adult patients in southeast England

There is a paucity of epidemiological data on chronic myeloproliferative disorders and myelodysplastic syndromes (MDS), while subtypes of acute myeloid leukemia (AML) are rarely defined. We identified 2,112 adult myeloid malignancies in the South Thames area between 1999 and 2000. The incidence (European standard population) of AML was 3.00/100,000, that of MDS 3.47/100,000, chronic myelomonocytic leukemia (CMML) 0.46/100,000, idiopathic myelofibrosis (IMF) 0.37/100,000, polycythemia vera (PV) 1.08/100,000, primary thrombocythemia (PT) 1.65/100,000 and chronic myeloid leukemia (CML) 1.09/100,000. The 3-year survival for AML was 15%, MDS 45%, CMML 29%, IMF 48%, PV 80%, PT 81% and CML 50% We believe this study reflects the true incidence and outcome of myeloid malignancies in South East England.     

Bone marrow trephine morphology and immunohistochemical findings in chronic myelomonocytic leukaemia

Chronic myelomonocytic leukaemia (CMML) is a clonal disorder with myelodysplastic/myeloproliferative features. Its diagnosis is based on the presence of peripheral blood monocytosis and bone marrow aspirate findings, according to World Health Organization criteria. However, bone marrow trephine biopsy (BMTB) features characteristic of CMML have not been adequately investigated. We studied BMTB in 20 cases of CMML-1 and three cases of CMML-2 and compared with ten cases of polycythaemia vera, ten cases of chronic myeloid leukaemia (chronic phase) and ten cases of florid myeloid hyperplasia (MH). Furthermore, we evaluated the use of CD34, CD117 and CD68 (PGM-1) antibodies in diagnosis and subtyping of CMML and in differentiating from other categories. Hypercellularity, high myeloid:erythroid ratio, increased proportion of 'myelo/monocytic' cells often seen as clusters and/or nodules, absence of eosinophilia, and presence of abnormal localisation of immature precursors (ALIP) and dysmegakaryopoiesis can aid in the diagnosis of CMML in BMTB. CD68 (PGM-1) positive cells amounted to 20·7 ± 6·1% cells among CMML trephines. The proportion of CD34⁺ cells among cases of CMML-1 was ≤5% and among CMML-2 was ≥10% cells in two of three cases and 5% in the other case. Morphological and immunohistochemical features of BMTB samples are extremely helpful in the diagnosis of CMML.     

Bone marrow histological changes in myelodysplastic syndrome and its clinical significance]

The authors compared bone marrow histological changes in 28 cases of myelodysplastic syndrome (MDS), 21 cases of aplastic anemia and 8 cases of hemolytic anemia. It is shown that abnormal localization of immature precursors (ALIP) is a characteristic change in MDS. The presence of erythroblastic islands and the variance of morphology of megakaryocytes are valuable for diagnosis. The histological method for the observation of lymphoid micromegakaryocytes is not so accurate as cytological method. "ALIP" can more or less help to evaluate the prognosis of MDS. According to the histological changes, it is easy to differentiate the three types of anemia we studied.     

Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes

Somatic mutation of the N-ras oncogene occurs frequently in de novo acute myeloid leukemia (AML). By virtue of their relation to AML, myelodysplastic syndromes (MDS) provide an in vivo model of human leukemogenesis. By using a strategy for analysis of gene mutation based on in vitro amplification of target sequences by the polymerase chain reaction (PCR) and selective oligonucleotide hybridization we analyzed the mutational status of codons 12, 13, and 61 of Ha-ras, K-ras, and N- ras in peripheral blood (PB) and/or bone marrow (BM) in 34 cases of primary MDS. Mutations at codon 12 of Ki-ras or N-ras were detected in three cases (9%): one of six cases of refractory anemia with excess blasts (RAEB) and two of nine cases of chronic myelomonocytic leukemia (CMML). The nucleotide substitution differed in each. In all cases the mutant allele was detectable in PB cells. A sustained hematologic remission was achieved after low-dose cytarabine therapy in the case of RAEB. Neither case of CMML exhibited signs of disease progression during follow-up at 7 and 12 months. In contrast, four of 31 patients without the ras mutation underwent transformation to AML within 12 months of genetic analysis. We conclude that ras mutations in MDS are heterogeneous and may develop at an early stage during the evolution of MDS. Their detection in PB cells illustrates the potential utility of ras mutation as a clonal marker in myeloid malignancy.     

Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies

TET2 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies including MDS, CMML, MPN, and AML. However, little is known regarding the biological function of TET2 and its role in the pathogenesis of myeloid malignancies. To study the function of TET2 in vivo, we generated a Tet2 knock out mouse model. Deletion of Tet2 in mice led to dramatic reduction in the 5-hydroxymethylcytosine levels and concomitant increase in the 5-methylcytosine levels in the genomic DNA of BM cells. The Tet2(-/-) mice contained an increased Lin(-)Sca-1(+)c-Kit(+) (LSK) cell pool before the development of myeloid malignancies. A competitive reconstitution assay revealed that Tet2(-/-) LSK cells had an increased hematopoietic repopulating capacity with an altered cell differentiation skewing toward monocytic/granulocytic lineages. Approximately 1/3 of Tet2(-/-) and 8% of Tet2(+/-) mice died within 1 year of age because of the development of myeloid malignancies resembling characteristics of CMML, MPD-like myeloid leukemia, and MDS. Furthermore, transplantation of Tet2(-/-), but not wild-type (WT) or Tet2(+/-) BM cells, led to increased WBC counts, monocytosis, and splenomegaly in WT recipient mice. These data indicate that Tet2-deficient mice recapitulate patients with myeloid malignancies, implying that Tet2 functions as a tumor suppressor to maintain hematopoietic cell homeostasis.     

Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: a clinicopathological study

BACKGROUND: The histopathologic features characterizing the involvement of the bone marrow (BM) in systemic lupus erythematosus (SLE) have not been systematically analyzed to date. OBJECTIVES: The aim of this study was to assess morphologic and immunohistochemical characteristics of BM involvement in SLE. PATIENTS AND METHODS: Clinical and serological data of 40 SLE patients with unexplained cytopenias were studied. Ten patients with myelodysplasia of refractory anemia (RA) were used as controls. BM aspiration, BM biopsy (BMB), and immunohistochemistry were carried out in patients and controls. BM fibrosis, BM necrosis, stromal edema, and abnormal localization of immature precursors (ALIP) were assessed according to standard criteria. RESULTS: Dyserythropoiesis and megakaryocytic atypias were uniform findings in SLE patients. The disruption of the normal BM architecture was a predominant SLE BM feature affecting cells of all three hemopoietic lineages, with both erythroid and megakaryocytic precursors tending to assume paratrabecular locations and ALIP aggregates being present in 27 cases. In addition, BM was hypocellular in 23 cases. BM necrotic alterations were evident in 90% of the cases. The density of reticulin content was generally increased. Vascular changes including dilatation of sinuses were manifest and were associated with the presence of necrotic alterations (P = 0.008). Hemoglobin levels correlated inversely with the presence of ALIP (P = 0.016). Upon comparing BMB features between SLE and RA controls there were striking similarities. CONCLUSIONS: BMB in patients with SLE and unexplained cytopenias presents a variety of histopathologic findings including BM necrosis, stromal alterations, hypocellularity, dyspoiesis, and distortion of normal BM architecture, characterized primarily by the presence of ALIP aggregates.     

The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy.

In human ovaries, angiogenesis is known to be associated with the development of follicles and the formation of the corpus luteum (CL). A complex vascular network is formed within the thecal cell layer during follicular growth, and rapid neovascularization occurs toward the granulosa cell layer after ovulation. Vascular endothelial growth factor (VEGF) is a multifunctional cytokine, stimulating endothelial cell growth and enhancing microvascular permeability. A specific receptor for VEGF, fms-like tyrosine kinase (Flt-1), is expressed in vascular endothelial cells that mediates the action of VEGF. We examined the localization and expression of VEGF and Flt-1, using an immunohistochemical technique and RT-PCR analysis, in human follicles and corpora lutea during the normal menstrual cycle and early pregnancy. We measured concentrations of VEGF in extracts of human CL using an enzyme-linked immunosorbent assay during the luteal phase and early pregnancy. Immunostaining for VEGF was observed in granulosa cells from small antral follicles to preovulatory follicles. The staining was detected in thecal cells from medium-sized to preovulatory follicles. The intensity of the staining was gradually increased as a follicle grew. Flt-1 was localized in granulosa and thecal cells of preovulatory follicles as well as in endothelial cells. In the human CL, the intense staining for VEGF was observed in granulosa and thecal lutein cells, especially in the midluteal phase. The immunostaining for Flt-1 was faint in endothelial cells in the CL, whereas it was distinct in granulosa and thecal lutein cells. The concentrations of VEGF in lutein extracts were high in the early and midluteal phases and tended to decrease toward the late luteal phase. During early pregnancy, a measurable amount of VEGF was detected. RT-PCR analysis demonstrated that messenger ribonucleic acids encoding VEGF121, VEGF165, and Flt-1 were expressed in the CL. These results suggest that VEGF might have an autocrine role in the ovulatory process and luteal function as well as a paracrine role in angiogenesis.     

Transformation of chronic myelomonocytic leukemia to acute lymphoblastic leukemia: Case report and review of the literature of lymphoblastic transformation of myelodysplastic syndrome

If chronic myelomonocytic leukemia (CMML) transforms into an acute leukemic phase, the blast crisis is invariably myeloid. Occasionally, the other subtypes of myelodysplastic syndrome (MDS) (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation) have been noted to transform into acute lymphoblastic leukemia (ALL). We now report a case of CMML that transformed into ALL and we review the literature of 13 other cases of MDS with ALL transformation. Such cases provide suggestive clinical evidence that MDS can involve a pluripotent stem cell. © 1955 Wiley-Liss, Inc.     

CD34 immunohistochemistry of bone marrow biopsies: Prognostic significance in primary myelodysplastic syndromes

Bone marrow (BM) biopsies from 58 patients with primary myelodysplastic syndrome (MDS) were studied using QBEND10, a monocional antibody that recognizes the human progenitor CD34 antigen in routine aldehyde-fixed paraffin-embedded samples. FAB subtypes were RA (5 patients), RARS (9 patients), RAEB (20 patients), RAEBt (11 patients), CMML (3 patients). In addition, 10 MDS patients whose BM biopsies revealed heavy reticulum fibrosis were included. Neither the percentage of CD34⁺ cells nor the number of CD34⁺ aggregates (defined as clusters of 3 or more cells) correlated with the presence and morphology of abnormal localizations of immature precursors (ALIP). When all patients were considered, median survival was 69 months in those with less, and 25 months in patients with more than 1% CD34⁺ cells (P < 0.05). Median survival was 15 months in patients with CD34⁺ aggregates and 41 months in those without aggregates (P = 0.0017). When RAEB patients were considered median survival was 41 months in those with less than 1%, and 29 months in those with more than 1% CD34⁺ cells; the 4-year survival chance was 45% in the former and 18.3% in the latter group. Therefore, CD34 positivity of more than 1% identifies a subset of RAEB patients with shorter life expectancy. In addition, leukemic transformation was observed in 11 of 35 patients (31%) with no CD34 aggregates, but in 14 of 23 patients (60%) with aggregates (P < 0.05). CD34 immunostaining, which can be easily performed on routinely prepared BM biopsies, was found to be a powerful prognostic tool for predicting survival and outcome in MDS. © 1994 Wiley-Liss, Inc.     

CMML: a biologically distinct myeloproliferative disease

Chronic myelomonocytic leukemia (CMML) is a myeloproliferative disorder with unique characteristics. Dysplasia is usually present in the bone marrow, thus CMML has usually been classified as a myelodysplastic syndrome. The recent World Health Organization classification of myeloid malignancies proposes to classify CMML into a new category of myelodysplastic syndromes and myeloproliferative disorders. A new prognostic score has also been developed exclusively for patients with CMML that recognizes four groups with distinct prognoses. Significant biologic findings in the recent months include the recognition of the importance of angiogenesis in CMML with a possible autocrine role for vascular endothelial growth factor, and the further understanding of the role of tyrosine kinase fusion genes and activation in some patients with CMML Therapeutic discoveries have been hampered by the paucity of studies looking specifically at CMML Among agents with potential significant activity are imatinib mesylate (for patients with platelet-derived growth factor beta receptor-associated fusion genes), hypomethylating agents, antiangiogenic agents, farnesyltransferase inhibitors, and topoisomerase I inhibitors. Future studies should consider CMML as a separate entity to promote a better understanding and identify more effective therapy for patients with this disease.     

Myelodysplastic syndromes: analysis of 131 cases according to the FAB classification

The clinical and haematological findings in 131 patients with myelodysplastic syndromes (MDS), none of which had previously received chemotherapy or radiotherapy, classified according to the FAB criteria, were analysed. The distribution among the 5 subgroups was: RA 31 patients, RAS 19, RAEB 23, CMML 29 and RAEBT 29 patients. There were difficulties in the classification of 24 patients. These included, first, 8 cases with myeloid hyperplasia of the bone marrow (BM) but without monocytosis or excess of blasts of the BM. They were classified as RA. Second, 8 cases with sideroblastosis but with monocytosis or excess of blasts of the BM were classified 3 as RAEB, 2 as CMML and 3 as RAEBT. Finally, 8 cases with absolute monocytosis and BM blasts 15-30% were classified as CMML. 37 of 82 dead patients (45.1%) had transformed to acute non-lymphoblastic leukaemia (ANLL). The incidence of evolution to ANLL was low for RA and RAS (6.30% and 12.5% respectively), while it was 37.5% for RAEB, 57.1% for CMML and 77.2% for RAEBT. The median survival for each subgroup was: RA 18 months; RAS 25; RAEB 13; CMML 14 and RAEBT 10 months. It is concluded that the FAB classification with some modifications recognises group of MDS with different prognosis.     

WT1 gene expression: useful marker for minimal residual disease in childhood myelodysplastic syndromes and juvenile myelo‐monocytic leukemia?

The WT1 gene is considered to be highly expressed in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia and is thought to play a key role in maintaining the viability of leukemia cells. However, little is known about the WT1 gene expression levels in pediatric patients with juvenile myelo-monocytic leukemia (JMML) and myelodysplastic syndromes (MDS). We studied WT1 expression in diagnostic bone marrow (BM) and peripheral blood (PB) samples of 90 patients with JMML, low grade MDS, advanced MDS and myelodysplasia-related AML in BM (n = 20) and PB (n = 18) samples of normal healthy volunteer donors.