Prevalence and clinical characteristics of myelodysplastic syndrome with bone marrow eosinophilia or basophilia

By retrospectively analyzing 288 patients with de novo myelodysplastic syndrome (MDS), we sought to determine the prevalence and clinical characteristics of bone marrow eosinophilia and basophilia that were detected at presentation. Bone marrow eosinophilia and basophilia were defined as a differential count of each cell type exceeding 5.0% and 1.0%, respectively. Of 288 patients with MDS, 36 (12.5%) fulfilled this criterion for bone marrow eosinophilia (MDS-Eos); 34 patients (11.8%) showed basophilia (MDS-Bas), and 11 (3.8%) satisfied both criteria (MDS-EosBas). The remaining 229 patients had neither eosinophilia nor basophilia in their bone marrow (MDS(-/-)) at presentation. Cytogenetic analysis was carried out on unstimulated bone marrow cells obtained from 264 patients. When the cytogenetic categorization of the IPSS (International Prognostic Scoring System) for MDS was applied, significantly higher numbers of MDS-Eos and MDS-Bas patients had chromosomal abnormalities carrying intermediate or poor prognosis, compared with the MDS(-/-) patients. Specific chromosomal abnormalities and complex karyotypes were associated with MDS-Eos and/or MDS-Bas. In accordance with these results, the overall survival rate was significantly lower, and the evolution to acute myelogenous leukemia (AML) occurred more frequently in the MDS-Eos and MDS-Bas than in the MDS(-/-) patients. Multivariate analysis demonstrated that bone marrow basophilia was an independent risk factor for evolution to AML. Our study indicates that bone marrow eosinophilia and basophilia in patients with MDS predict a poorer prognosis.     

Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors

It is known that alkylating agents and topoisomerase II inhibitors can cause distinct forms of therapy-related leukemia and myelodysplastic syndrome (TRL/MDS). Although several reports have been made on each of these agents separately, no study has yet been conducted to evaluate the effect of these two types of agents in the same population. In a nationwide, large-scale population study, the clinical and cytogenetic features as well as the prognostic factors in 256 patients with TRL/MDS were assessed. Median age was 61 years, and the median period of latency from primary malignancies was 47.9 months. The latency period was significantly shorter in patients undergoing chemotherapy, especially that of topoisomerase II inhibitors, for primary cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia in 59% and MDS in 41% of patients. Chromosome abnormalities that frequently involved chromosomes 5, 7 or 11 were documented in 77% of the 189 patients examined. MLL gene rearrangements were detected in 11 of 58 subjects and were correlated with a borderline significance (P = 0.072) with topoisomerase II inhibitor administration. Overall median survival was only 9.7 months. Survival was similar in cases with or without MLL gene rearrangement. Multivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, poor therapy outcomes for primary cancer, C-reactive protein, and thrombocytopenia as being significantly poor prognostic factors (P < 0.05). This large-population study provided a comprehensive update of TRL/MDS status in Japan, identified significant prognostic factors, and enabled the clinical significance of MLL gene rearrangement to be assessed.     

Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy. The myelodysplastic phase, with or without evolution to acute leukemia, is a highly lethal disease with a median survival comparable to that of the patients who present with AML.     

Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia

Nineteen patients with high-risk myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) received fludarabine, cytarabine, granulocyte-colony stimulating factor (G-CSF), and idarubicin chemotherapy ( de novo MDS/MDS-AML, nine; relapsed/refractory MDS/AML, seven; therapy-related MDS, three). Median age was 44 years and median disease duration 10 months. 16/19 (84%) patients had abnormal cytogenetics with seven (37%) harbouring abnormalities of chromosome 7. 18/19 (94.7%) patients responded to FLAG-idarubicin with 12 (63%) achieving complete remission (CR) (<5% blasts and normal cytogenetics). 7/9 (78%) patients with de novo MDS/MDS-AML achieved CR compared to 5/10 (50%) with alternative diagnoses. Response was associated with age < 50 years, disease duration < 3 months, and cytogenetics other than abnormalities of chromosome 7. Haemopoietic regeneration was rapid in most patients and there were no toxic deaths. Nine patients received a second course of chemotherapy, three have proceeded to allogeneic bone marrow transplant and three to autologous blood stem cell/bone marrow transplantation. Follow-up is short (median 10 months). 12/19 (63%) patients remain alive and 5/12 (42%) have relapsed at a median 5 months following CR achievement. FLAG-idarubicin was well tolerated. High rates of morphological and cytogenetic remission, especially in de novo MDS, offer a window of opportunity for assessment of autologous BMT in this group of diseases where no treatment except alloBMT has led to prolongation of survival.     

Redefining monosomy 5 by molecular cytogenetics in 23 patients with MDS/AML

Deletion of the long arm of chromosome 5 [del(5q)] or loss of a whole chromosome 5 (-5) is a common finding, arising de novo in 10% of patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and in 40% of patients with therapy-related MDS or AML. We investigated by molecular cytogenetics 23 MDS/AML patients for whom conventional cytogenetics detected a monosomy 5. Monosomy 5 was redefined as unbalanced or balanced translocation and ring of chromosome 5. Loss of 5q material was identified in all 23 patients, but one. One copy of EGR1(5q31) or CSF1R(5q33-34) genes was lost in 22 of the 23 patients. Chromosome 5p material was a constant chromosomal component of derivative chromosomes or rings in all patients, but one. Sequential fluorescent in situ hybridization studies with whole chromosome paints and region-specific probes, used as a complement to conventional cytogenetic analysis, allow a better interpretation of karyotypes in MDS/AML patients.     

Comparison between interphase and metaphase cytogenetics in detecting chromosome 7 defects in hematological neoplasias

Monosomy 7 (–7) is one of the most common chromosomal abnormalities found in the leukemic cells of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Because patients with –7 have a poor prognosis, their identification is important for treatment planning. Conventionally, –7 is detected by the G-banding technique. This study examines the use of fluorescent in situ hybridization (FISH) methodology to detect –7 cells in interphase nuclei and metaphase chromosomes. Fifteen AML or MDS patients whose leukemic cells were found to have –7 by G-banding at disease presentation were studied. In 13 of these patients, –7 could be detected in interphase by FISH using a chromosome 7-specific centromeric DNA probe. The two patients whose leukemic cells were not detectable by interphase FISH had –7 and t(1q;7p), which were detectable by FISH in metaphase using a chromosome 7-specific painting probe. Metaphase FISH was particularly useful in further defining chromosome 7 defects in cells that contained aberrant or marker chromosomes. For example, in 6 patients, chromosome 7 sequences were detectable in aberrant or marker chromosomes by metaphase FISH, but not by G-banding. These results suggest that metaphase FISH is an important adjunct to conventional cytogenetic methods for defining chromosome 7 abnormalities in AML and MDS patients. Furthermore, interphase FISH is useful for follow-up studies in patients who are found informative for the FISH study at presentation.     

Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the Q arm of chromosome 3

Summary To determine the frequency and clinical significance of acquired abnormalities of chromosome 3 at q21 and q25–26 in haematological malignancy, we reviewed the haematological and cytogenetic features of 24 patients with a 3q rearrangement identified amongst 1200 cases with clonal cytogenetic abnormalities detected at our institutions during a 12-year period. Thirteen patients presented with de novo acute myeloid leukaemia (AML), 10 with myelodysplasia (MDS) and one in blast phase of chronic myelogenous leukaemia. Twenty patients (83%) had megakaryocytic dysplasia and 14 (58%) had normal or increased numbers of megakaryocyte, but only four patients (16%) had absolute thrombocytosis > 500 × 10⁹/l (three with AML, one with MDS transforming to AML).
A review of 205 cases of AML investigated in our institutions between 1985 and 1990 for whom cytogenetic results were obtained revealed that a platelet count > 500 × 10⁹/l at presentation was highly suggestive of an underlying 3q abnormality. A limited review of the literature on this subject confirmed that 15-20% of patients with a 3q abnormality will have thrombocytosis. The response of these patients to conventional antileukaemic therapy is uniformly poor, despite haematological and clinical differences between the subtypes of 3q rearrangements.     

骨髓增生异常综合征克隆性8号染色体三体和7号染色体缺失的发生及其临床意义

目的：了解＋8和-7／7q-克隆在骨髓增生异常综合征（MDS）中的发生情况，探讨＋8和-7／7q-克隆在MDS发生发展中的可能机制及其临床意义。方法：采用短期培养法和G显带技术，对MDS患者的染色体异常、尤其＋8和-7／7q～核型进行分析。结果：70例原发性MDS患者中，有43例存在染色体异常，异常检出率为61．4％，最常见的染色体异常为＋8（18例）和-7／7q-（8例），其中4例为＋8与-7／7q-并存。＋8克隆多出现在RA阶段，而-7／7q-克隆则出现在疾病进展中。伴有-7／7q-核型的MDS，更容易转化为白血病。结论：＋8和-7／7q-核型仍是MDS最为常见的染色体异常。＋8克隆出现在MDS的早期，可能与Fas介导的细胞凋亡有关；而-7／7q-克隆的形成，导致MDS的进展及向白血病转化，可能与丢失片段的抑癌基因的失活有关。     

Comparative genomic hybridization study of de novo myeloid neoplasia

Comparative genomic hybridization (CGH) was used to detect chromosomal imbalances in 20 patients with a diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). The results obtained were compared with G-banding analysis. This last methodology showed 50% of cases with clonal abnormalities whereas CGH detected 70% of cases with copy number changes. Gains were more frequent than losses and constituted 66% of total changes detected. The most common gains included chromosomes 21 and chromosome region 18p for AML and chromosome 17 and region 1p33p35 for MDS. Losses represent 34% of changes and the regions involved were 5q31q32, 7q22, 7p12 and 13q21q22. CGH revealed additional chromosome imbalances in 12 of 20 cases (60%) which were not detected by traditional cytogenetic studies, demonstrating complex karyotype in 50% (6/12). Combination of CGH and G-banding provides an efficient method to identify critical regions present in the malignant clone, which is of great value in the prognosis and outcome of myeloid neoplasias.     

Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities

Acute Myeloid Leukemia (AML) and myelodysplasia (MDS) with chromosome 3q abnormalities have a dismal outcome either untreated or with conventional treatments. Azacitidine (AZA) is now considered as the standard of care in high‐risk MDS and oligoblastic AML patients. The objective of this study was to evaluate the impact of azacitine treatment in this cytogenetic subgroup. We report here a multicentre retrospective study of 157 patients treated with AZA for AML/MDS with chromosome 3q abnormalities and 27 patients with isolated EVI‐1 overexpression. Median age was 65 years, 40 patients (25%) had inv(3)(q21q26.2) or t(3;3)(q21;q26.2), 36 patients (23%) had other balanced 3q26 rearrangements, 8 patients (5%) had balanced 3q21 rearrangements and 73 patients (46%) had other 3q abnormalities. The overall response rate was 50% (29% CR). Median overall survival was 10.6 months. By multivariate analysis, patients with lower bone marrow blast counts, higher platelet counts, non‐complex cytogenetics, and absence of prior treatment with intensive chemotherapy had a better outcome. 27 patients were allo‐transplanted and achieved a 21‐month median OS. Balanced 3q21 translocations were associated with a better response rate and overall survival. Outcome of patients with isolated EVI‐1 overexpression was comparable to that of patients with chromosome 3q lesions. Thus, AML/MDS patients with 3q abnormalities appear to be a heterogeneous group in their response to AZA, and AZA may represent a suitable option in particular as a bridge to allogeneic transplantation. Am. J. Hematol. 90:859–863, 2015. © 2015 Wiley Periodicals, Inc.     

Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera

A minor fraction of patients with polycythemia vera (PV) develop a terminal acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Analysis of the cytogenetic abnormalities during AML or MDS may help in understanding if this development is part of the natural course of the disease or induced by myelosuppressive therapy. Thirty-six cases with AML or MDS post PV, collected in a single Swedish institution during a 33-year period, are described with special regard to time to development of AML or MDS, therapy given during active PV, and cytogenetic findings during AML or MDS. A further 118 cases of AML or MDS post PV, in whom type of therapy during active PV and cytogenetic findings during AML or MDS were reported, were collected from the literature. AML or MDS developed in our own series after 1–30 years with a fairly constant rate (two cases per year). The most frequent cytogenetic abnormalities were +1q, −5, 5q−, −7, 7q−, +8, +9, 11q−, 13q−, and 20q−. When patients in the total material (n = 154) were divided with regard to treatment during active PV, marked differences were observed. The highest frequency of abnormalities was found in patients given multiple lines of therapy (n = 61), dominating features being −5/5q− in 28 patients (46%), −7/7q− in 19 patients (31%), numerous translocations in 24 patients (39%), and unidentified markers in 22 patients (36%). Half of the patients treated with hydroxyurea alone showed a −5 or 5q− abnormality. In patients treated with phlebotomy alone, +8 and +9 were the most frequent findings. The type of therapy given during active PV influences the type of chromosome abnormalities present during terminal AML or MDS and can also be instrumental in the development of leukemia.     

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.     

der(1;7) (q10;p10) in three patients with malignant hematologic disorders]

The chromosome der(1;7) (q10;p10) is a derivative chromosome consisting of the short arm of chromosome 7 and the long arm of chromosome 1. We observed this abnormality in three patients with acute myeloblastic leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD). Case 1 was a 76-yr-old male with a history of IgG myeloma treated with melphalan, cyclophosphamide, vincristine, and prednisolone (MEVP). AML-M1 developed one and half years after discontinuation of the MEVP therapy. Case 2 was a 39-yr-old male with MDS. Case 3 was a 56-yr-old male with refractory anemia with excess of blasts in transformation that evolved from primary myelofibrosis. Chromosome analyses revealed der(1;7) (q10;p10) in bone marrow cells of the three patients. All patients failed to respond to chemotherapy, and died within four months after the diagnosis. Thus, der (1;7) (q10;p10) may indicate a very poor prognostic outcome in patients with malignant hematologic disorders.     

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.     

Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy

We have studied 20 children with therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were 3 months to 16 years old at diagnosis of their primary neoplasm and 1 to 24 years old at diagnosis of their secondary neoplasm. The median interval from initial treatment for the first malignancy to diagnosis of therapy-related MDS or AML was 46 months (range, 12 to 116 months). Twelve patients had chromosomal abnormalities resulting in loss of material from the long arm of chromosomes 5 and/or 7, three patients had abnormalities of chromosome 11 band q23, one patient had both classes of abnormalities, three patients had other abnormalities, and one patient had a normal karyotype. Ten of 12 patients with chromosome 5 and/or 7 abnormalities had been exposed to an alkylating agent, and two of three patients with 11q23 abnormalities had been exposed to an epipodophyllotoxin. The patient with both classes of abnormalities had been exposed to both types of therapy. We conclude that abnormalities of chromosomes 5 and/or 7 are common in children with therapy-related MDS or AML. The proposed relationships between exposure to alkylating agents and abnormalities of chromosomes 5 and/or 7 and between exposure to epipodophyllotoxins and abnormalities of 11q23 are supported in this pediatric series.     

Follow-up by cytogenetic and fluorescence in situ hybridization analysis of allogeneic bone marrow transplantation in two children with Fanconi's anaemia in transformation

Results of bone marrow transplantation (BMT) in patients with Fanconi's anaemia (FA) in transformation are very poor and only a few cases with favourable outcome have been reported. We present the follow-up of two FA-myelodysplastic syndrome (MDS) patients with monosomy 7 and complex karyotype implicating chromosome 1. Both relapsed with acute myeloid leukaemia (AML) following an allogeneic BMT from an HLA-identical brother. The patients showed clonal cytogenetic evolution coinciding with the leukaemic transformation. In one patient, fluorescence in situ hybridization using X and Y chromosome probes detected an increase of host cells before clinical relapse. Both patients received a successful second allogeneic BMT from the same donor using a more intensive treatment regimen and remain in clinical and cytogenetic remission more than 3 years later.     

3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features.

BACKGROUND AND OBJECTIVE: Acute myeloblastic leukemia (AML) with features of myelodysplastic syndrome (MDS) and abnormalities of megakaryocytopoiesis is often characterized by cytogenetic aberrations of the 3q21 and 3q26 bands involving inv(3)(q21q26) and (3;3)(q21;q26). These aberrations have been described in all FAB subtypes with the exception of M3, and in MDS and in megakaryoblastic crisis of chronic myeloid leukemia. We reviewed the biological and clinical features of 10 cases of AML with inv(3)(q21q26) and t(3;3)(q21;q26). DESIGN AND METHODS: Four hundred and sixteen patients with AML were studied in our Institute by cytogenetic analysis and 10 (2.4%) showed inv(3)(q21q26) (7 patients) or t(3;3)(q21;q26) (3 patients): 7 males, 3 females; median age, 43.5 yrs. We also used RT-PCR to investigate the pattern of expression of the EVI-1 gene in 5 patients. RESULTS: Additional chromosomal changes were demonstrated in 6 patients. In 5/10 cases a preceding MDS had been observed. A possible occupational exposure was established in 2 patients (a farmer and an histologist employing organic solvents) and another patient had a therapy-related leukemia. AML subtype was M1 in 9 patients and M2 in 1. A variable excess of micromegakaryocytes was observed in all the patients. In 5 patients the platelet count was normal or increased (median number: 172. 5x10(9)/L; range 55-440). Expression of EVI-1 gene was present in all the 5 patients studied. The clinical course and outcome was extremely poor: 9/10 patients were resistant and 1 patient showed a partial remission after induction therapy. Of the 9 patients resistant to the first line chemotherapy, 7 were also resistant to the second line chemotherapy. Three patients obtained a morphologic complete remission after third line chemotherapy (duration 1, 3 and 6 months); 2 of them were submitted to autologous bone marrow transplantation, but relapsed after 1 and 3 months. The median overall survival was 5.5 months. INTERPRETATION AND CONCLUSIONS: Our findings evidence a strong correlation between 3q21q26 chromosomal aberrations, abnormalities of megakaryocytopoiesis and lack of response to conventional chemotherapy and support the diagnostic and prognostic relevance of chromosome characterization in the classification of AML.     

Three cases of the myelodysplastic syndrome with pericentric inversion of chromosome 16

Summary. Inversion of chromosome 16, inv(l6)(pl3q22), is characteristic of acute myeloid leukaemia (AML) with eosinophilia and is rarely found in the myelodysplastic syndrome (MDS). We report three cases of MDS in which inv(16) was observed. They were classified to FAB subtypes RA. RAKS and KAEBT: eosinophilia or abnormal eosinophils were not observed. The disease appeared to be stable in all three patients. MDS with inv(16) without eosinophilia may be a rare subgroup associated with a good prognosis.     

骨髓增生异常综合征435例WHO分型和细胞遗传学分析

目的 探讨我国骨髓增生异常综合征(MDS)WHO亚型分布和细胞遗传学异常特点,并与西方国家进行比较.方法 采用前瞻性方法收集了协作组435例MDS患者,进行WHO分型,采用染色体G显带和荧光原位杂交(FISH)技术进行细胞遗传学分析.结果 MDS中位发病年龄为58(18～90)岁.难治性血细胞减少伴多系发育异常(RCMD)病例比例最高,约占69.6%(303/435),其他亚型依次为难治性贫血伴原始细胞增多(RAEB)24.1%(105/435)、难治性贫血(RA)2.3%(10/435)、不能分类MDS(MDS-U)2.3%(10/435)、难治性贫血伴环状铁粒幼细胞增多(RAS)1.2%(5/435)和5q-综合征0.5%(2/435),而西方国家RA、RAS、5q-综合征比例较高,RCMD亚型比例低于中国.11例染色体检查失败,424例染色体检查成功的染色体克隆性异常率为38.7%(164/424),其中RAEB-Ⅰ异常率最高62.5%(25/40),其次RAEB-Ⅱ 48.4%(30/62)、RCMD 34.5%(102/296).常见的染色体异常依次为:+8为12.7%(54/424)、复杂核型为9.O%(38/424)、染色体易位为7.8%(33/424)、-20q为6.6%(28/424)、-7/-7q为5.2%(22/424)、-5/-5q为4.2%(18/424),而国外最常见的是-5/-5q、-7/-7q、+8、11q及12p/12q异常.以国际预后积分系统染色体预后分组,染色体预后良好组68.2%(289/424),预后中等组19.1%(81/424),预后不良组12.7%(54/424).有17例患者因为异常细胞的比例偏低,染色体检查正常,但FISH检测到低水平的异常.结论 我国MDS的WHO亚型分布与染色体异常分布与西方国家不同.FISH和常规染色体检查相结合,可以提高检测的灵敏度.     

Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia

OBJECTIVE: Bone marrow mesenchymal stroma cells (BMSC) are key components of the hematopoietic microenvironment. The question of whether BMSC from patients with hematological disorders have cytogenetic abnormalities is discussed controversially, some studies indicating that they are cytogenetically normal and others providing evidence of their aberrations. PATIENTS AND METHODS: We performed standard and molecular cytogenetic analyses of both hematopoietic cells and BMSC from 31 patients with myelodysplastic syndrome (MDS, n = 18) and acute myeloid leukemia (AML, n = 13) and 7 healthy individuals. Mononuclear cells were isolated from fresh bone marrow aspirates at the time of initial diagnosis for cytogenetic analysis of hematopoietic cells (HC) and selection of BMSC. RESULTS: Clonal cytogenetic aberrations were observed in HC from 8 (44%) MDS and 8 (61%) AML patients. Cytogenetic analyses of BMSC were successfully performed in 27 of the 31 cases. Structural chromosomal aberrations, including t(1;7), t(4;7), t(7;9), t(7;10), t(7;19), t(15;17), and others, were detectable in BMSC from 7 of 16 (44%) MDS and 6 of 11 (54%) AML patients. The breakpoints of chromosomes in BMSC were typical for leukemia aberrations. Two patients showed clonal chromosomal markers. CONCLUSIONS: BMSC from MDS and AML patients show chromosomal abnormalities. Although the majority of cytogenetic aberrations in BMSC were not clonal and differed from chromosomal markers in HC from the same individual, detection of typical chromosomal changes in BMSC suggests enhanced genetic susceptibility of these cells in MDS/AML. This may indicate potential involvement of BMSC in the pathophysiology of MDS/AML.