Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin''s lymphomas on fine needle aspiration cytology

Non-Hodgkin's lymphomas (NHL) are tumours of the lymphoid cells. During the process of development of lymphoid cells, neoplasia may evolve at any point. Neoplastic cells usually carry the imprint of cell of origin at the stage of origin. Various types of NHL may have similar morphology with wide variation in origin, immunophenotype and other biological features. Different ancillary laboratory techniques may help to overcome the limitations of morphology in this aspect. The commonly used ancillary techniques in lymphomas are immunocytochemistry (IC), flow cytometry, Southern blot (SB) technique, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In addition, laser scanning cytometry (LSC) and DNA microarray technologies are in the research phase. Various laboratory techniques are used for immunophenotyping, demonstration of monoclonality, identification of chromosomal translocation, assessment of cell kinetics and expression of mRNA in the tumour cells. Flow cytometry helps in rapid immunophenotying of NHL and it has an added advantage over IC in recognizing the co-expression of CD markers. Fine needle aspiration cytology (FNAC) combined with flow immunophenotyping may help us to diagnose and subclassify certain NHLs, such as follicular lymphoma and mantle cell lymphoma, which were previously recognized as pure morphological entities. Loss of morphology is one of the important limitations of flow cytometry. LSC can overcome this limitation by studying morphology along with the immunophenotyping pattern of individual cells. Chromosomal changes in NHL can be identified by SB, PCR and FISH. Molecular diagnosis of NHL helps in diagnosis, subclassification, prognostic assessment and even in planning of therapy. DNA microarray is a relatively newer and promising technology. It gives information about the expression of several thousands of genes in a tumour in a single experiment. In the near future, FNAC combined with ancillary techniques may play a major role in diagnosis, subclassification and management of lymphomas.     

Gray zones around diffuse large B cell lymphoma. Conclusions based on the workshop of the XIV meeting of the European Association for Hematopathology and the Society of Hematopathology in Bordeaux, France

The term “gray-zone” lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and Epstein–Barr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panel’s proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters.     

Cytogenetics in malignant lymphoma.

There appear to be four primary areas of interest in the application of cytogenetic techniques to the study of malignant lymphomas: (1) the role of cytogenetics in the diagnosis of lymphoma in problem cases, (2) as an aid to the classification of malignant lymphomas, (3) whether specific chromosomal patterns will have prognostic significance for response to therapy or survival, and (4) the role of cytogenetics in staging of malignant lymphomas. A case of reactive lymphoid hyperplasia is reported in which cytogenetic studies demonstrated an aneuploid clone suggesting that cytogenetic abnormalities of lymphoma may precede the diagnostic histopathologic picture. The occurrence of 14q+ marker chromosomes in plasmacytic myeloma, plasma cell leukemia, malignant lymphomas, Burkitt's lymphoma, and ataxia-telangiectasia suggest that a common etiologic or pathogenetic mechanism may be present in some of these disorders. A preliminary pilot study of spleens removed at staging laparotomy for Hdgkin's disease suggests that cytogenetic studies may be able to detect Hodgkin's disease that is not apparent histologically. Further studies are required to provide answers to these areas of interest in cytogenetics in malignant lymphoma.     

Leukocyte-common antigen and vimentin are reliable adjuncts in the diagnosis of non-Hodgkin's lymphoma in fine needle aspirates

Alcohol-fixed fine needle aspirates of 82 non-Hodgkin's malignant lymphomas (NHLs) were tested for the presence of vimentin and leukocyte-common antigen (LCA) by means of monoclonal antibodies (MAbs) and indirect immunofluorescence. All NHLs stained positively for vimentin; the staining was strong in all except three cases. Of the 69 NHLs tested for LCA, 1 (a large cell T-cell lymphoma) was negative while the staining was weak in 6. Thus, vimentin and LCA MAbs are sensitive, specific and reliable complementary diagnostic adjuncts that are useful in the definitive diagnosis of NHLs in alcohol-fixed fine needle aspirates. Their presence in the aspirate confirmed a cytologic diagnosis of NHL in 47 cases, helped to diagnose NHL in 31 cases in which a cytologic differential diagnosis with small cell anaplastic carcinoma could not be made with confidence and helped to change the initial cytologic diagnosis of anaplastic carcinoma to NHL in 4 cases.     

Expression of the CD31 antigen in normal B-cells and non Hodgkin's lymphomas

The role cell adhesion molecules play in the biological and clinical behaviour of non Hodgkin's lymphomas (NHL) has been reported in several studies. This study reports the findings on B-cells taken from various healthy control tissues and compared them to B-cells from 83 malignant B-lymphomas, that had been classified according to the WHO classification. Flow cytometry was used to investigate the surface expression of CD31, an adhesion molecule involved in B-cell development and vascular adhesion mechanisms. Quantification of the fluorescence signals showed specific patterns of CD31 expression on normal B-cell subpopulations and different NHL groups. Our results demonstrate that CD31 expression is modulated during the differentiation process in normal B-cells, high in pre-B-I cells, low in pre-B-II precursors, intermediate in the mature B-cell subpopulations or, depending on the functional state absent in activated follicular centre cells, present in pre- and post- germinal centre cells. When the CD31 expression is evaluated as fluorescence intensity in NHL, it reveals a heterogeneous pattern related to histogenetic derivation (high in small lymphocytic lymphoma, low in follicular lymphoma, intermediate in marginal zone and large cell lymphomas). These observations suggest that CD31 might well play a critical role in the ontogeny and physiology of B-lymphocytes. Therefore, on the basis of these observations we propose the CD31 molecule as an interesting additional useful parameter to be used for the differential diagnosis of NHL and hypothese that it has a pathophysiologic role in NHL evolution.     

Analysis of serum proteome profiles of non-Hodgkin lymphoma for biomarker identification

Serum samples from non-Hodgkin lymphoma (NHL) patients who had not undergone chemotherapy, lymphnoditis patients, and healthy adults were analyzed using surface-enhanced laser desorption–ionization time-of-flight mass spectrometry (SELDI-TOF MS) to detect the differentially expressed serum proteins. Models were developed to distinguish between the healthy adult group and the NHL group, with a sensitivity of 69% and specificity of 90%, and between the lymphnoditis group and the NHL group with a sensitivity of 74% and specificity of 84%. A protein with the m/z of M10 197.91 u was expressed at a significantly higher level in the NHL group, compared to the other groups. Furthermore, differences were also significant among different stages of NHL and among samples with different International Prognosis Index (IPI) scores or lactase dehydrogenase (LDH) levels. The three identified proteins may offer a new serological approach for early diagnosis, differential diagnosis, and pathogenic investigation of NHL. And the protein with the m/z of M10 197.91 u may be a new serological biomarker for monitoring treatment response and evaluating the prognosis of patients with NHL.     

Primary non-Hodgkin's lymphoma of the breast: a case report

Extranodal non-Hodgkin's lymphoma (NHL) of the breast is a rare entity. It represents 0.04-1.1% of malignant tumors of the breast. 1.7-2.2% of extranodal lymphomas and 0.7% of all NHL. However, primary NHL (PNHL) is the most frequent hematopojetic tumor of the breast. CASE: A 23-year-old woman presented with a mass in the left breast for 3 months followed by enlarged left axillary lymph nodes. Mammography showed a diffuse increase in the density of the left breast. Other investigations were unremarkable. Both fine needle aspiration cytology (FNAC) and histopathology were diagnostic of NHL. Immunohistochemistry was confirmatory of NHL, diffuse large cell type, of B-cell lineage. CONCLUSION: Primary and secondary lymphomas of the breast, though rare, should be considered in the differential diagnosis of breast malignancies. PNHL of the breast is usually right sided, but this patient had left breast involvement. Diagnosis by FNAC was successful as the cytologic picture is similar to that of any other lymphoid or extranodal NHL. When histopathology and immunohistopathology are conclusive, FNAC, supplemented by immunocytochemistry, can be applied as a simple, reliable and cost-effective tool in the early diagnosis of breast lymphomas.     

Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.     

AIDS-related body cavity-based lymphoma. A case report

BACKGROUND: Body cavity-based lymphomas are rare malignancies in human immunodeficiency virus (HIV)-infected patients, but because of their unusual clinical, morphologic and immunophenotypic features, they are recognized as a distinct subgroup of lymphomas connected to human herpesvirus 8 (HHV-8) infection. CASE: A 39-year-old, HIV-positive, homosexual man was admitted to the hospital because of a left-sided pleural effusion that contained malignant lymphoid cells. He responded partially to a low-dose cyclophosphamide/doxorubycin/vincristine/prednisone regimen and died five months after the diagnosis of lymphoma. On cytology, the sediments contained exclusively large, round, neoplastic, lymphoid cells with abundant basophilic cytoplasm and large, round nuclei with prominent nucleoli. Many cells had immunoblastic features, and some had plasmocytoid differentiation. Mitotic figures were numerous. On flow cytometry, the homogeneous population of large cells expressed CD45, CD38, HLA-DR and CD7 positivity. Other specific T-, B- and NK-cell markers tested negative. Polymerase chain reaction demonstrated Epstein-Barr virus (EBV) and HHV-8 in the malignant effusion. CONCLUSION: Primary effusion from lymphoma with molecular evidence of HHV-8 and EBV coinfection represents a distinct clinical and morphologic entity in AIDS patients. However, immunophenotypic markers of malignant clones can be diverse in different cases.     

Novel miRNA markers for the diagnosis and prognosis of endometrial cancer

As endometrial cancer (EC) is a major threat to female health worldwide, the ability to provide an accurate diagnosis and prognosis of EC is promising to improve its treatment guidance. Since the discovery of miRNAs, it has been realized that miRNAs are associated with every cell function, including malignant transformation and metastasis. This study aimed to explore diagnostic and prognostic miRNA markers of EC. In this study, differential analysis and machine learning were performed, followed by correlation analysis of miRNA‐mRNA based on the miRNA and mRNA expression data. Nine miRNAs were identified as diagnostic markers, and a diagnostic classifier was established to distinguish between EC and normal endometrium tissue with overall correct rates >95%. Five specific prognostic miRNA markers were selected to construct a prognostic model, which was confirmed more effective in identifying EC patients at high risk of mortality compared with the FIGO staging system. This study demonstrates that the expression patterns of miRNAs may hold promise for becoming diagnostic and prognostic biomarkers and novel therapeutic targets for EC.     

CHOP-firstline treatment in NHL with unfavorable prognosis--evaluation of therapeutic response and factors influencing prognosis

58 NHL-patients (9 large cell centrocytic, 18 centroblastic, 16 immunoblastic, 15 lymphoblastic lymphomas) were treated immediately after diagnosis with CHOP-chemotherapy regardless of the extent of disease. Because of the advanced age of the majority of patients (median age 61 years, range 22-85 years) a reduced dose in the first two cycles was administered. Statistically significant prognostic variables influencing survival were the following: histologic subtypes according to the Kiel-classification (p less than 0,05), B-symptoms (p less than 0,001), blood sedimentation rate (p less than 0,02) and LDH (p less than 0,0005). With regard to prognosis there was no difference between patients over 60 years of age and younger ones (p less than 0,4). Patients achieving complete remission survived significantly longer (p less than 0,0001). Ann Arbor stages were of limited value, since patients with CS II disease and accumulation of risk factors (B-symptoms, abdominal disease, bulky tumor masses) showed a poorer outcome than patients with CS III who did not have these risk factors. A risk factor score summarizing features influencing prognosis is described and might be a useful tool in stratifying the heterogeneous group of NHL with unfavorable prognosis.     

TGF-beta1 gene polymorphisms influence the course of the disease in non-Hodgkin's lymphoma patients

Non-Hodgkin's lymphomas (NHL) constitute a heterogenous group of mainly B-cell lymphoproliferative diseases with different patterns of clinical behaviour. Biological mechanisms leading to development of NHL are not clearly understood. Transforming growth factor-beta1 (TGF-beta1) influences B cell growth and development. The present study aimed to determine whether there is an association between the polymorphic features located within the TGF-beta1 gene in NHL patients and progression of the disease. Two single nucleotide polymorphisms at positions 869 T/C (Leu10Pro) and 915 G/C (Arg25Pro) in the precursor region of the TGF-beta1 gene were determined in 55 NHL patients and 50 healthy individuals by PCR-SSP technique using commercial primers. In univariate analysis the presence of TGF-beta1 high producer genotypes (T/T G/G or T/C G/G) was found to significantly associate with an increased number of extranodal sites (11/30 vs 3/25, p=0.035 for two or more extranodal sites in patients having or lacking the TGF-beta1 high producer genotype, respectively). TGF-beta1 high producer genotype together with other clinical and biological factors (patient sex and age, stage and aggressiveness of the disease, presence of B symptoms, serum LDH level) were subjected to multivariate logistic regression analyses for the number of extranodal sites. Multivariate analysis confirmed the role of TGF-beta1 high producer genotype as a risk factor of NHL manifestation in two or more extranodal sites (OR=7.217, p=0.043) in addition to histological aggressiveness of the disease (OR=4.302, p=0.057). TGF-beta1 gene polymorphisms were found to associate with the course of the disease in NHL patients. TGF-beta1 high producer genotype appeared as an independent risk factor of extranodal manifestation of the disease.     

Role of molecular markers in diagnosis and prognosis of renal cell carcinoma

It has been demonstrated that different renal cell neoplasms have characteristic morphologic and genetic features. Histologic subtyping of renal epithelial neoplasms has been shown to be of prognostic value; therefore they must be correctly classified. Although adequate sampling and a good understanding of the morphologic features usually minimize diagnostic errors, the use of immunohistochemical and chromosomal analysis on formalin-fixed, paraffin-embedded tissues can be necessary. These techniques can facilitate diagnosis on small biopsies, which are increasingly obtained from renal masses. An immunohistochemical panel including CD10, parvalbumin, AMACR, CK7 and S100A1 seems the most promising; fluorescence in situ hybridization analysis using centromeric probes to evaluate the gains and losses of the chromosomes can be helpful in selected cases. A wide variety of molecular markers have been examined, but further research is required to prove their value as prognostic tools.     

Management of localized non-Hodgkin's lymphoma

Non-Hodgkin''s lymphomas (NHLs) are a heterogeneous group of disorders that vary widely in response to therapy. In Canada the modified Rappaport classification is used to categorize NHL. To facilitate the reporting and comparison of treatment results all cases should also be categorized in the terminology of the National Cancer Institute''s working formulation. The choice of therapy should be guided by specific prognostic factors: stage and bulk of the disease, patient''s age, presence of systemic symptoms and histologic subtype. Of these, the last appears to be the most important. Radiotherapy (RT) is the treatment of choice in localized low-grade lymphomas with favourable prognoses, while bimodal therapy (RT and chemotherapy [CT]) is warranted in presentations with unfavourable prognoses. Regional irradiation alone is indicated in intermediate-grade lymphomas with good prognoses (i.e., pathological stage I or II or clinical stage IA or IIA localized disease of small bulk in young patients). All other patients require CT followed by RT. The results of CT alone are encouraging but remain experimental. Aggressive therapy with multidrug regimens that include central nervous system prophylaxis is the foundation for successful treatment of high-grade NHL such as lymphoblastic lymphoma and diffuse small-noncleaved-cell lymphomas. Low-dose RT should be given to sites of bulky disease.     

Contribution of flow cytometric immunophenotyping to the evaluation of tissues with suspected lymphoma?

BACKGROUND: A critical analysis of the contribution of flow cytometric immunophenotyping (FCI) to the evaluation of lymph nodes and extranodal tissues with suspected lymphoma by a large, retrospective approach has not been reported previously and represents the purpose of this study. METHODS: A total of 278 lymph nodes and 95 extranodal tissue specimens submitted over a 2-year period with complete histologic, FCI, and immunohistochemical (IH) data formed the basis of the study. RESULTS: The FCI data contributed significantly to or was consistent with the final tissue diagnosis in the majority (94%) of the tissue samples. There is no well-described utility of flow cytometry markers for Hodgkin's lymphoma (HL) due to the usual scarcity of tumor cells in the final cell suspensions obtained from these tumors. However, the FCI data excluded non-Hodgkin's lymphoma (NHL) and suggested the possible usefulness of CD15 and CD30 by FCI in HL. In addition, immunophenotypic data by FCI in combination with touch imprint cytomorphology was useful in excluding a diagnosis of NHL in cases of nonhematopoietic malignancies and was particularly useful in defining the following hematopoietic tumors and malignancies: thymoma, T-cell lymphoblastic lymphoma, leukemia cutis, and plasma cell dyscrasia. Thus, IH was not essential for the diagnosis in these latter cases and was performed in only two cases (one thymoma and one plasma cell dyscrasia). Of interest, FCI supported the diagnosis in 3 cases of Ewing's sarcoma/primitive neuroectodermal tumor by detection of CD56 on the surface of the malignant cell. Only 11% of NHL were "negative" by FCI (i.e., an aberrant T-cell or monoclonal B-cell population was not identified). Reasons for these discrepancies included partial tissue involvement by the NHL with sampling differences, T-cell rich or lymphohistiocytic-rich variants with a small population of monoclonal B cells, marked tumoral sclerosis, poor tumor preservation, and T-cell NHL without an aberrant immunophenotype. Only 60% of CD30+ anaplastic large cell lymphomas (ALCL) were CD30+ by FCI. CONCLUSIONS: FCI data should always be correlated with light microscopy if no FCI abnormalities are detected; IH may need to be performed in selected cases. It is less necessary to perform microscopic examination of tissues when the FCI data are positive and indisputable. However, in selected cases in which FCI data is diagnostic, microscopic observations may provide additional information due to sampling.     

Molecular pathology in the diagnosis and treatment of non-Hodgkin's lymphomas

The non-Hodgkin's lymphomas encompass a wide spectrum of hematologic neoplasms that exhibit different clinical and biological features. Lymphomas classically have been initially assessed based on their cytologic and histologic features. Morphology alone is often inadequate as similar appearing neoplasms may be immunophenotypically and molecularly heterogeneous. Molecular diagnostic methods can provide an additional level of testing that not only helps refine diagnoses but can provide prognostic information. New methods are being refined that may provide information to establish precise diagnostic profiles, provide targets for therapy and provide more sensitive methods for monitoring the success of treatment. Molecular methods will be increasingly utilized and eventually required as the accepted method of diagnosis and for monitoring the disease. Understanding of the molecular abnormality and the pathogenesis of the neoplasm hopefully will lead to therapeutic intervention aimed at the specific molecular defect or its product. The molecular pathology of the non-Hodgkin's lymphomas is discussed.     

Long non-coding RNA as a novel biomarker and therapeutic target in aggressive B-cell non-Hodgkin lymphoma: A systematic review

Cancer initiation and progression have been associated with dysregulated long non-coding RNA (lncRNA) expression. However, the lncRNA expression profile in aggressive B-cell non-Hodgkin lymphoma (NHL) has not been comprehensively characterized. This systematic review aims to evaluate the role of lncRNAs as a biomarker to investigate their future potential in the diagnosis, real-time measurement of response to therapy and prognosis in aggressive B-cell NHL. We searched PubMed, Web of Science, Embase and Scopus databases using the keywords “long non-coding RNA”, “Diffuse large B-cell lymphoma”, “Burkitt's lymphoma” and “Mantle cell lymphoma”. We included studies on human subjects that measured the level of lncRNAs in samples from patients with aggressive B-cell NHL. We screened 608 papers, and 51 papers were included. The most studied aggressive B-cell NHL was diffuse large B-cell lymphoma (DLBCL). At least 79 lncRNAs were involved in the pathogenesis of aggressive B-cell NHL. Targeting lncRNAs could affect cell proliferation, viability, apoptosis, migration and invasion in aggressive B-cell NHL cell lines. Dysregulation of lncRNAs had prognostic (e.g. overall survival) and diagnostic values in patients with DLBCL, Burkitt's lymphoma (BL), or mantle cell lymphoma (MCL). Furthermore, dysregulation of lncRNAs was associated with response to treatments, such as CHOP-like chemotherapy regimens, in these patients. LncRNAs could be promising biomarkers for the diagnosis, prognosis and response to therapy in patients with aggressive B-cell NHL. Additionally, lncRNAs could be potential therapeutic targets for patients with aggressive B-cell NHL like DLBCL, MCL or BL.     

Exploration of DNA methylation markers for diagnosis and prognosis of patients with endometrial cancer

The accurate diagnosis of endometrial cancer (EC) holds great promise for improving its treatment choice and prognosis prediction. This work aimed to identify diagnostic biomarkers for differentiating EC tumors from tumors in other tissues, as well as prognostic signatures for predicting survival in EC patients. We identified 48 tissue-specific markers using a cohort of genome-wide methylation data from three common gynecological tumors and their corresponding normal tissues. A diagnostic classifier was constructed based on these 48 CpG markers that could predict cancerous versus normal tissue with an overall correct rate of 98.3% in the entire repository. Fifteen CpG markers associated with the overall survival (OS) and development of EC were also identified based on the methylation patterns of the EC samples. A prognostic model that aggregated these prognostic CpG markers was established and shown to have a higher discriminative ability to distinguish EC patients with an elevated risk of mortality than the FIGO staging system and several other clinical prognostic variables. This study presents the utility of DNA methylation in identifying biomarkers for the diagnosis and prognosis of EC and will help improve our understanding of the underlying mechanisms involved in the development of EC.     

成人t(8;21)急性髓系白血病患者初诊Ki-67的表达特征及预后意义

目的:研究成人t(8; 21)急性髓系白血病(AML)初诊Ki-67抗原的表达特征及预后意义。方法:采集2012年7月至2019年2月本院57例成人初诊t(8; 21) AML患者的新鲜骨髓标本,采用流式细胞术(FCM)检测CD34和Ki-67抗原,分析Ki-67表达与患者初诊生物学特征、疗效及复发的关系。结果:全部患者中,CD34~+Ki-67~+细胞比例的中位值为30. 5%(范围:10. 0%～65. 8%);通过受试者工作特征(ROC)曲线确定CD34~+Ki-67~+细胞比例的最适分界阈值,CD34~+Ki-67~+细胞高比例与初诊c-KIT基因突变阳性及WT1转录本低水平均明显相关(P=0. 001; P=0. 042)。随访的36例患者中,CD34~+Ki-67~+高比例比低比例患者具有明显更高的1年累积复发(CIR)率(P=0. 035);此外,初诊WT1转录本低水平和微小残留病(MRD)高水平(2个疗程巩固治疗后RUNX1-RUNX1T1转录本水平下降3-log)均与更高的1年CIR率明显相关(P 0. 0001;P=0. 041),初诊c-KIT基因突变阳性和白细胞计数 10×109/L的患者分别有较高的1年CIR率趋势(P=0. 091; P=0. 054)。联合分组显示,MRD高水平同时CD34~+Ki-67~+细胞高比例的患者比其他患者具有明显更高的1年CIR率(P 0. 0001)。结论:初诊骨髓高比例的CD34~+Ki-67~+可能是成人t(8; 21) AML患者预后不良因素,MRD联合初诊CD34~+Ki-67~+细胞比例可能比单纯MRD更好地预测复发。