几种血液病骨髓幼稚前体细胞异位的组织学观察

采用塑料包埋改良的苏木素伊红加姬母萨氏染色及ＬＳＡＢ免疫组化技术对２８例骨髓增生异常综合征（ＭＤＳ）（ＲＡ１２例，ＲＡＥＢ１０例及ＲＡＥＢ－Ｔ６例）和７６例非ＭＤＳ（巨幼细胞性贫血，ＭＢＡ６例，ＡＩＨＡ１０例，ＰＮＨ１０例，ＭＦ１０例，ＰＶ１０例，ＩＴＰ１０例，ＰＲＣＡ１０例，ＣＡＡ１０例）患者骨髓活检中的ＡＬＩＰ现象作了研究，发现ＡＬＩＰ现象不是ＭＤＳ骨髓组织所特有的。除ＭＤＳ骨髓切片阳性（≥３     

Immunotyping of blasts in refractory anaemia with excess of blasts

Summary. A study of immunological markers was performed in 16 patients with newly diagnosed refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) and in 12 other patients with acute myeloid leukaemia evolving from RAEB or RAEB-T. Immunocytochemical investigation of bone marrow blasts was done using a modified indirect immunoperoxidase technique. This method permitted accurate morphological identification of blasts and other cells in bone marrow. The monoclonal antibodies used in RAEB and RAEB-T samples were anti-CD34, -c-kit, -HLA-DR and -CD13.
The range of CD34 expression of blasts in RAEB samples was 1–14% (mean 6·2%) and in RAEB-T samples 29–48% (mean 35·5%). CD34 positivity was detected in 3·94% (mean 47·4%) of the bone marrow blasts in acute myeloid leukaemia evolving from RAEB and RAEB-T. Expression of c-kit was demonstrated only in a low percentage of blast cells in RAEB, RAEB-T and acute myeloid leukaemia following myelodysplasia. A high percentage (> 30%) of blasts in most patients with RAEB, RAEB-T and acute myeloid leukaemia was HLA-DR and CD13 positive. We observed the transformation from RAEB to acute myeloid leukaemia in three patients. The proportion of CD34 positive blasts increased to 25% and 32% in two patients. The third patient showed an unchanged percentage of CD34 positivity of blasts.
These findings indicate that the CD34 positivity of blasts increases with the progression of myelodysplasia to RAEB-T and acute myeloid leukaemia demonstrating the instability of the clonal defect in myelodysplasia.     

All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study

Considering the beneficial effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), it has been speculated that ATRA might also be useful for treating other hematologic malignancies. To test this hypothesis, we performed a dose-escalating 3-month-trial of ATRA in 15 patients with primary or secondary myelodysplastic syndromes (MDS). Morphologic diagnoses were refractory anemia (RA) in 4, RA with ring sideroblasts (RARS) in 2, RA with excess blasts (RAEB) in 7, and RAEB in transformation (RAEB/T) in 2 cases. Patients included were required to have one or more of the following criteria: transfusion- dependent anemia, pronounced neutropenia (< or = 0.5 x 10(9)/L) or thrombocytopenia (< or = 20 x 10(9)/L), or increasing blast cells in the peripheral blood or bone marrow. Therapy was started at an ATRA dose of 30 mg/m2/d, administered orally as two doses of 15 mg/m2 every 12 hours. The retinoid dose was increased to 60 mg/m2/d after 4 weeks and to 90 mg/m2/d after 8 weeks. Among 14 patients assessable for response, none obtained a complete or partial remission. Three patients had a minor response, manifested by either reduction in transfusion requirements (2 patients) or increase in neutrophil and platelet counts (1 patient). During the study period, 5 patients progressed to more advanced stages of MDS or overt leukemia. Three patients with chromosomal abnormalities receiving ATRA for a period of 10 to 12 weeks retained their cytogenetic marker after completion of treatment. Side effects of ATRA primarily affected the skin and mucous membranes, with 13 of 15 patients having at least low-grade dermatologic toxicity. In 2 cases, treatment had to be prematurely stopped because of intolerable conjunctivitis or progressive neurologic symptoms. These data suggest that ATRA has little effect on MDS. The lack of response of MDS patients, as compared with those with APL, may be attributed to the absence of the t(15;17) translocation that seems to be a prerequisite for clinical efficacy of ATRA.     

Differential cellular expression of the human MSH2 protein in normal and myelodysplastic haematopoiesis

Loss of human MSH2 (hMSH2) protein might be involved in the multistep pathogenesis of haematological malignancies associated with genetic instability. Here, we examine cellular hMSH2 expression in bone marrow samples from 10 haematopoietically normal individuals in comparison with nine patients with myelodysplastic syndrome (MDS) [one refractory anaemia (RA), two RA with ringed sideroblasts (RARS), four RA with excess blasts (RAEB) and two RAEB in transformation (RAEB-T)]. HMSH2 protein was predominantly expressed in myeloblasts and promyelocytes. Blast cells from three patients with RAEB and one with RAEB-T displayed absent or very low hMSH2 expression. As no correlation between hMSH2 expression and chromosomal aberrations was observed, further genetic events seem to be required to induce karyotype instability.     

Expression and prognostic significance of Bcl-2 family proteins in myelodysplastic syndromes

Excessive apoptosis is implicated in the pathogenesis of myelodysplastic syndromes (MDS). We assessed by flow cytometry the expression of several members of the Bcl-2 family in bone marrow mononuclear cells (BMMNC) of 168 MDS samples at diagnosis. The proteins studied were Bcl-2, Bcl-xL (anti-apoptotic), Bax, Bad, Bak, and Bcl-xS (pro-apoptotic). The percentage of BMMNC expressing Bcl-2 and Bcl-xL was higher in refractory anemia with excess of blasts (RAEB), RAEB in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMML) than in refractory anemia (RA) and RA with ringed sideroblasts (RAS). Conversely pro-apoptotic proteins Bad, Bak, and Bcl-xS were detected in a higher percentage of cells in RA and RAS. RA and RAS were associated with an increased Bcl-xS/Bcl-xL ratio. The expression of anti-apoptotic proteins was also correlated with that of CD34 and P170 and with the percentage of blast cells. Two-color analyses demonstrated that CD34 and Bcl-2 were usually expressed in the same cells. No significant correlation was found with cytogenetic abnormalities. Higher expression of pro-apoptotic Bcl-2-family proteins (Bak, Bad, Bcl-xS) and higher Bcl-xS/Bcl-xL ratio were associated with longer survival and decreased risk of leukemic transformation in univariate analysis, whereas expression of anti-apoptotic proteins was associated with decreased survival. Consequently Bcl-2 proteins expression was well correlated with the International Prognostic Scoring System (IPSS). Our data confirm that the control of apoptosis is deregulated in MDS cells. Moreover, the study of markers such as CD34 (or Bcl-2), Bcl-xL, and Bcl-xS provides additional prognostic information.     

Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience

The purpose of this study was to evaluate the role of allogeneic bone marrow transplantation (BMT) in children with myelodysplastic syndrome (MDS). In total, 94 consecutive pediatric patients with MDS received an allogeneic BMT from 1976 to 2001 for refractory anemia (RA) (n=25), RA with ringed sideroblasts (RARS) (n=2), RA with excess blasts (RAEB) (n=20), RAEB in transformation (RAEB-T) (n=14), juvenile myelomonocytic leukemia (JMML) (n=32) or chronic myelomonocytic leukemia (CMML) (n=1). The estimated 3-year probabilities of survival, event-free survival (EFS), nonrelapse mortality and relapse were 50, 41, 28 and 29%, respectively. Patients with RA/RARS had an estimated 3-year survival of 74% compared to 68% in those with RAEB and 33% in patients with JMML/CMML. In multivariable analysis, patients with RAEB-T or JMML were 3.9 and 3.7 times more likely to die compared to those with RA/RARS and RAEB (P=0.005 and 0.004, respectively). Patients with RAEB-T were 5.5 times more likely to relapse (P=0.01). The median follow-up among the 43 surviving patients is 10 years (range 1-25). We conclude that allogeneic BMT for children with MDS is well tolerated and can be curative.     

Donor lymphocyte infusion to treat relapse after allogeneic bone marrow transplantation for myelodysplastic syndrome

Donor lymphocyte infusion has become established as a salvage therapy for patients with hematological disorders relapsing after allogeneic bone marrow transplantation (BMT). The role of donor lymphocyte infusion for patients with myelodysplastic syndrome (MDS) remains to be established. Between July 1993 and October 2001, 14 patients with MDS relapsing after allogeneic BMT received DLI as salvage therapy. At the time of BMT, one patient had RA, nine had RAEB, of whom three were in CR after induction-type chemotherapy, two had RAEB-T, one had CMML and one had AML. Donors were HLA-matched siblings (n=12), HLA-matched other relative (n=1) and unrelated (n=1). At the time of relapse, the median marrow blast count was 9%. The median CD3+ cell dose administered was 6.3 x 10(7)/kg. With a median follow-up of 49 months, six patients were alive, of whom two were in CR after DLI alone and remained disease-free, two were in CR after a second BMT and two had active disease. Eight patients died of disease progression. Although DLI alone seems to be effective in a small number of patients with MDS, other treatment strategies, including prior debulking chemotherapy, deserve investigation.     

Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.     

Evaluation of apoptosis as a prognostic factor in myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hypercellular bone marrow. This is thought to be as a result of the apoptosis of haematopoietic bone marrow cells resulting in ineffective haematopoiesis. To clarify the relationship between prognosis and apoptosis and/or cell proliferation in the bone marrow, we studied 51 cases with MDS. Bone marrow biopsies were stained immunohistochemically for MIB-1 (marker for proliferating cells) and CD34 (marker for stem cells). Apoptosis was visualized by detection of DNA fragmentation using TdT incorporation of nucleotides on 3' ends of DNA (TUNEL technique) and expressed as the apoptotic rate. MDS patients included 32 with refractory anaemia (RA), one RA with ringed sideroblasts (RARS) patient, seven RA with excess of blasts (RAEB) patients, eight patients with RAEB in transformation (RAEB-t) and three patients with chronic myelomonocytic leukaemia (CMMoL). In addition, we also studied six cases with acute myeloid leukaemia (AML) arising from MDS (AML-MDS) and ten control subjects. Fatal pancytopenia was the cause of death in 19 out of 51 patients. The apoptotic rate was higher in MDS patients (5.5%) than in control subjects (0.6%) and AML-MDS patients (0.4%). The percentage of MIB-1 positive cells was higher in MDS and AML-MDS than in control. The percentage of CD34-positive cells was higher in AML-MDS, RAEB, RAEB-t and CMMoL patients than control subjects and RA patients. Our findings indicate the activation of both the proliferative and apoptotic rates in MDS. Poor prognosis correlated significantly with higher apoptotic rates, but not with percentages of MIB-1 and CD34-positive cells. Our results suggest that apoptosis might be a useful prognostic factor and inhibition of apoptotic mechanisms may induce leukaemic transformation in MDS.     

Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia

The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomono-cytic leukaemia, CMMoL). Mean s-TK levels (U//tl) measured at diagnosis were 11–9 –12–6 for RA, 11–4–13'6 for RARS, 19–9 – 28–4 for RAEB, 39–6 – 34–3 for RAEB-T and 77–7 – 69–7 for CMMoL (normal values <5U//LI1). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK >38 V/fA , a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK <38U//xl (8–2 v 37–4 months, respectively; P < 0–0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK >38U//d and 9/69 (13%) of those with lower levels at diagnosis (P < 00001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.     

Leukocyte-derived inhibitory activity in patients with myelodysplastic syndrome

Summary Leukocyte-derived inhibitory activity inhibiting the entry of normal progenitor cells of granulocytes and macrophages (CFU-GM) into the S-phase of a cell cycle was investigated in 16 patients with different forms of myelodysplastic syndrome (MDS). The presence of this inhibitory activity was analysed in medium conditioned with low-density cells obtained from peripheral blood of MDS patients. The inhibition rate was measured by ³H-thymidine suicide technique with subsequent cultivation of pretreated cells in semisolid agar medium. Low-density cells from MDS patients of various types were studied: from the twelve patients with refractory anaemia (RA or RAS) only three were positive, one patient with chronic myelomonocytic leukaemia (CMML) was negative while one patient with refractory anaemia with excess of blasts (RAEB) and two patients with RAEB in transformation (RAEB-T) were positive with respect of the described test. In two patients with RA, who underwent a long-term investigation, the production of leukocyte-derived inhibitory activity preceded the development of disease into RAEB or RAEB-T. In five positive cases, supernatants were incubated with antiserum against human placental ferritin; with one exception, the inhibitory activity was neutralized.     

A clinical study on myelodysplastic syndrome. Report of 64 cases

Systematic clinical and laboratory observations of 64 cases of myelodysplastic syndrome (MDS) were made. The results showed that malignant clone already exists in the bone marrow of patients with MDS. Eighteen cases of them have transformed into AML. The rates of transforming into AML in RAEB, RAEB-T and CMML were markedly higher than that in RA. The courses of MDS which transformed into AML from the various types were different. The transformation in RA was obviously longer than those in RAEB and RAEB-T. Two cases transformed into myelofibrosis. Diagnosis of CMML according to the FAB classification criteria revealed that it has two forms. One shows only increase of mature monocytes and it has no relation with the types of acute leukemia to be transformed. It is considered as a reactive monocytosis. The other form, in addition to increase of mature monocytes, also has increase of a few monoblasts and promonocytes. These are considered as true CMML and usually quickly developed into M4 or M5 which are related with monocytes.     

Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations

The EVI1 gene encodes a zinc-finger, DNA-binding protein originally described as the transforming gene associated with a common ecotropic viral insertion site in myeloid leukemias. Previous studies demonstrated EVI1 expression in human leukemias in cases with 3q26 translocations, but not in normal blood or bone marrow. These studies also suggested an association between EVI1 expression and chromosome 7 deletion (del). Because of this association, we examined expression of EVI1 using RNA polymerase chain reaction (PCR) in patients with myelodysplastic syndromes (MDS) and acute leukemia with and without 3q26 translocations. EVI1 RNA was expressed in 29% of 34 (95% confidence interval, 20% to 50%) patients with the MDS subtypes refractory anemia (RA), refractory anemia with excess blasts (RAEB), or refractory anemia with excess blasts in transformation (RAEB-T). The vast majority of these cases occurred in patients with RAEB and RAEB-T. EVI1 expression was not detected in patients with chronic myelomonocytic leukemia (CMML), normal bone marrow or cord blood, or a variety of other hematologic malignancies. EVI1 RNA was detected in three of 18 patients with acute myelogenous leukemia (AML) and in two of four patients with acute promyelocytic leukemia (APL). Karyotypes showed that only one AML patient had karyotype 3q26 abnormalities, indicating that EVI1 expression is associated with cases that do not have structural abnormalities involving chromosome 3q26. These studies document for the first time the abnormal expression of EVI1 RNA by patients with MDS, and suggest an important role for EVI1 in the pathogenesis or progression of some myeloid malignancies.     

Myelodysplastic syndrome with eosinophilia in bone marrow

Summary. Clinical features were investigated in 114 patients with de novo myelodysplastic syndrome (MDS) diagnosed over the past 10 years, and eight cases (7%) were complicated with eosinophilia in the bone marrow. Two patients had refractory anaemia (RA), five had RA with excess of blasts (RAEB), and one had RAEB in transformation. Their bone marrow cells exhibited trilineage dysplasia and morphological abnormalities in eosinophils. Cytogenetics revealed major karyotype abnormalities (MAKA) in five patients. Survival durations were significantly shorter than those of other MDS patients. Our study suggests that marrow eosinophilia in MDS is strongly related to the coexistence of MAKA.     

骨髓增生异常综合征T细胞早期激活及可溶性肿瘤坏死因子受体的研究

目的　研究骨髓增生异常综合征 (MDS)外周血CD+ 4 、CD+ 8T细胞早期激活标志CD69的表达及血清、骨髓可溶性肿瘤坏死因子受体 1、2 (sTNF R1、2 )的水平及其意义。方法　在植物血凝素 (PHA) 2 0mg/L条件下进行全血细胞培养 ,于 0h和 4h分别用流式细胞仪对CD+ 4 、CD+ 8T细胞CD69的表达进行分析。用ELISA法检测血清和骨髓sTNF R1、2的水平。结果　PHA刺激前难治性贫血 (RA)与难治性贫血伴环形铁粒幼细胞增多 (RAS)CD+ 4 、CD+ 8细胞CD69的表达率分别为 8 32 %、9 88% ,难治性贫血伴原始细胞增多 (RAEB)与转变中的RAEB(RAEB T)CD+ 8细胞CD69的表达率为7 92 %。PHA刺激后MDS患者CD+ 4 、CD+ 8细胞表达CD69明显增强 ,RA +RAS为 5 3 4 6 %、5 1 6 3% ;RAEB +RAEB T为 4 2 93%、4 1 96 % ,CD+ 4 与CD+ 8细胞CD69的表达率相似。MDS两种sTNF R1水平均明显升高 ,RA +RAS组sTNF R1血清为 (1 5 8± 0 6 8) μg/L ,骨髓为 (2 10± 0 2 6 ) μg/L ;sTNF R2血清为 (1 4 1± 0 5 0 ) μg/L ,骨髓为 (1 95± 0 6 4 ) μg/L ;RAEB +RAEB T组sTNF R1血清为 (2 6 2± 2 5 5 ) μg/L ,骨髓为 (3 12± 0 6 7) μg/L ;sTNF R2血清为 (1 96± 0 5 6 ) μg/L ,骨髓为(3 0 9± 0 6 2 ) μg/L。血清sTNF R2水平与PHA刺激     

Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF.

Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics.     

The effect of stem-cell factor,interleukin-3 and erythropoietin on in vitro erythropoiesis in myelodysplastic syndromes

An inherent defect of erythroid differentiation at the colony-forming unit blast (CFU-blast) compartment and (or) an impaired response of early erythroid progenitors (BFU-E) to growth stimulation are both considered to contribute to anemia in myelodysplastic syndromes (MDS). With the intention of improving survival and growth of early erythroid progenitors we investigated the effect of stem-cell factor (SCF) and interleukin-3 (IL-3) alone and in combination with erythropoietin, on the in vitro erythropoiesis of 13 patients with MDS and of three normal controls. SCF and IL-3 alone did not promote erythroid colony growth in MDS, while 3 cases responded to erythropoietin alone. In each of these, BFU-E colony growth could be increased by SCF, which was also found in all normal bone marrows. Altogether 6 cases showed a significant enhancement of BFU-E colony numbers by the combination of SCF and erythropoietin as compared to erythropoietin alone (P=0.036). Out of the 6 responding cases, 5 belonged to the FAB-classified subgroups refractory anemia (RA) and refractory anemia with ringed sideroblasts (RA/RS) (5/5), while 1 patient was classified as having refractory anemia with excess of blasts (RAEB) (1/4). No patient with refractory anemia with excess of blasts in transformation (RAEB-T) (0/4) responded. In spite of these positive effects, the absolute number of BFU-E colonies remained reduced in all MDS cases when compared to normal controls. IL-3 proved ineffective in increasing the response to erythropoietin in MDS although it increased erythropoietin-induced BFU-E formation in normal controls significantly. We conclude that the striking synergistic effect of SCF and erythropoietin on erythroid colony formation seen with normal bone marrow is conserved in most cases with RA and RA/RS. In RAEB and RAEB-T the intrinsic defect of the erythroid differentiation pathway cannot be overcome by SCF.Abbreviation MDS myelodysplastic syndrome - SCF stem-cell factor - II-3 interleukin-3 - RA refractory anemia - RA/RS RA with ringed sideroblasts - RAEB RA with excess of blasts - RAEB-T RA with excess of blasts in transformation - Epo erythropoietin     

Vitamin K2 therapy for myelodysplastic syndrome

Vitamin K2 is reported to induce apoptosis or differentiation of leukemic cell lines in vitro. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to 23 patients with myelodysplastic syndrome (MDS): 13 patients with RA, 2 with RARS, 6 with RAEB and 2 with RAEB-T. Good response (GR) and partial response (PR) were defined as an increase of hemoglobin concentration exceeding 2 g/dl and 1-2 g/dl without transfusion, respectively. Six of the RA patients showed improvement of anemia (GR, 3 patients; PR, 3 patients). RA patients who did not have a hypocellular bone marrow and were transfusion-independent tended to be responsive to vitamin K2 therapy in combination with vitamin D3 or anabolic steroids. No adverse effect of vitamin K2 was observed, and the time required to obtain the hematological response was short, being 3 months on average. We believe that vitamin K2 therapy has potential as a treatment for patients with MDS.     

Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis

The International Prognostic Scoring System (IPSS) has been widely used to predict the prognosis of patients with myelodysplastic syndrome (MDS). However, IPSS does not always provide a sufficiently precise evaluation of patients to allow the appropriate choice of clinical interventions. Here, we analyzed the expression of Bmi-1, which is required to regulate the self-renewal in CD34+ cells from 51 patients with cases of MDS and acute myeloid leukemia preceded by MDS (MDS-AML). Higher positivity rate of Bmi-1 was preferentially seen in refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-T), and MDS-AML compared with refractory anemia (RA) and RA with ringed sideroblasts (RARS). IPSS score was positively correlated with the percentage of Bmi-1 expression. Patients with RA and RARS with a higher percentage of Bmi-1+ cells showed disease progression to RAEB. Here, we propose Bmi-1 as a novel molecular marker to predict the progression and prognosis of MDS.