With the popularity of flow cytometry, the classification of leukemia become more detailed. Myeloid/natural killer cell precursor acute leukemia and myeloid/natural killer cell acute leukemias are generally recognized as two kinds of rare leukemias and have poor prognosis. The cells expressed both myeloid and lymphatic antigens in these two leukemia and can not be diagnosed by morphology. The only basis to make a definite diagnosis is their unique Immunophenotyping. The role of CD7 and CD56 in these two leukemia are compelling, in the other hand, as the progress of cell differentiation research, there are many new awareness of NK cell differentiation. In this article, the biological origin, clinical manifestation, diagnosis, treatment and the role of CD7 and CD56 in these two leukemia are briefly summarized.
Antigens, CD7 ; CD56 Antigen ; Cell Differentiation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; classification ; diagnosis ; therapy

OBJECTIVETo study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions.

METHODSFormalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7.

RESULTSTwenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss.

CONCLUSIONLoss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.

Adolescent ; Adult ; Antigens, CD7 ; metabolism ; CD2 Antigens ; metabolism ; CD3 Complex ; metabolism ; CD5 Antigens ; metabolism ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Histiocytic Necrotizing Lymphadenitis ; immunology ; pathology ; Humans ; Male ; Middle Aged ; Pseudolymphoma ; immunology ; Recurrence ; T-Lymphocytes ; immunology ; Young Adult

OBJECTIVETo clarify clinical and morphological features and immunophenotype of T lymphoblastic lymphoma/leukaemia (T-LBL/ALL) and to further improve the knowledge and diagnostic accuracy for T-ALL/LBL.

METHODS128 cases of T-LBL/ALL were analyzed for the clinical features, morphology, immunophenotype and TCR gene rearrangement using routine eosin and haematoxylin stain, immunohistochemistry and polymerase chain reaction combining with the clinical findings.

RESULTSIn 128 cases of T-LBL/ALL, there were 94 male and 34 female. The ratio of male/female was 2.8:1. The age of patients ranged from 4 to 88 years, with an average of 27 years and a median of 22 years. Lymph nodes and extranodal areas were involved in 58/128 and 27/128 cases of T-LBL/ALL, respectively. The other 43 cases had involvement of both nodal and extranodal areas. Cervical node and mediastinum were involved in 74 cases and 43 cases, respectively. Diffuse growth pattern of tumor cells was predominant. Nodular growth pattern was seen only in a few cases. Most cases composed of small to medium-sized lymphoblasts, and other 7 cases showed a composition of large lymphoblasts. Tumor cells expressed TdT in 121/128 (94.5%) cases, CD34 in 48/98 (49.0%) cases, CD3 in 78/108 (72.2%) cases, CD7 in 104/108 (96.3%) cases, CD43 in 56/63 (88.9%) cases, CD79a in 5/70 (7.1%) cases, CD10 in 25/76 (32.9%) cases, CD99 in 58/60 (96.7%) cases and Pax-5 in 4/91(4.4%) cases. All of the cases were negative for MPO. A follow up data, ranging from 1 to 53 months, was obtained in 51/128 (39.8%) patients. The over all survival rate was 68.6% and the median survival time was 12 months. Under a similar condition of carrying a positive staining result on CD3 in tumor cells, there was a statistically significant difference between patients in the group of over 30 of age and that with the age ranging from 11 to 30. Patients associating with a CD10 positive staining of tumor cells showed also a shorter survival period. In addition, there were 4 out of 5 cases showing the presence of TCR gene rearrangement.

CONCLUSIONST-LBL/ALL are aggressive in behavior, associating mainly with enlarged cervical lymph nodes and masses in the mediastinum, occurring predominantly in children and young adults. Although small to medium-sized tumor cells with diffuse pattern were found in most cases, however, large-sized tumor cells and nodular pattern could also be obtained in a few cases. Immunohistochemistry staining particularly adoption of CD7, Pax-5, TdT, CD34 and Ki-67 stainings in combination are helpful of making a diagnosis for T-LBL/ALL. Analysis of TCR gene rearrangement will be helpful for the diagnosis of a few difficult cases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Antigens, CD7 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD3 Complex ; metabolism ; Child ; Child, Preschool ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Follow-Up Studies ; Gene Rearrangement, T-Lymphocyte ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neprilysin ; metabolism ; PAX5 Transcription Factor ; metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; metabolism ; pathology ; Survival Rate ; Young Adult

Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Antigens, CD ; metabolism ; Antigens, CD7 ; metabolism ; Antigens, Neoplasm ; metabolism ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD3 Complex ; metabolism ; CD5 Antigens ; metabolism ; CD52 Antigen ; Chromosome Aberrations ; Chromosome Deletion ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Glycoproteins ; metabolism ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; drug therapy ; genetics ; metabolism ; pathology ; Neoplasm Recurrence, Local ; Prednisone ; therapeutic use ; Receptors, CXCR3 ; metabolism ; Survival Rate ; Vincristine ; therapeutic use

BACKGROUND AND OBJECTIVEPrecursor T lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma. Myeloid antigen expression was found in some of the patients, and its clinical significance is worth studying. This study was to compare the clinical features, short-term efficacy and survival of T-LBL patients with or without myeloid antigen expression so as to evaluate its prognostic significance.

METHODSForty-five T-LBL patients, with a median age of 14 years, were treated at Sun Yet-sen University Cancer Center between January 2000 and July 2008. These patients were divided into myeloid antigen-positive group (My(+) group) and myeloid antigen-negative group (My(-) group) based on the flow cytometric (FCM) analysis in bone marrow or pleural fluid. Myeloid antigen expression and its correlation with the short-term efficacy and overall survival were assessed in the two groups.

RESULTSThere were 18 patients (40.0%) in the My(+) group and 27 (60.0%) in the My(-) group. The myeloid antigen expression was negatively correlated with the initial level of lactate dehydrogenase (LDH), but not with other clinical features. The remission rate was lower in the My(+) group than in the My(-) group (38.8% vs. 70.3%, P = 0.028). The 2-year overall survival rate was lower in the My(+) group than in the My(-) group (51.9% vs. 78.7%, P = 0.036). By age subgroup analysis, there were no differences in response and survival rate among children and adolescents with or without myeloid antigen expression. But the remission rate and the 2-year overall survival rate were significantly lower in adult patients with myeloid antigen expression than in patients without it. Univariate and multivariate analysis demonstrated that age and myeloid antigen expression were adverse prognostic factors.

CONCLUSIONMyeloid antigen expression is a predictor of a poor response to chemotherapy, and adverse prognostic factor in adult T-LBL, but not in children with T-LBL.

Adolescent ; Adult ; Age Factors ; Aged ; Antigens, CD7 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asparaginase ; therapeutic use ; Child ; Cyclin D3 ; metabolism ; Cyclophosphamide ; therapeutic use ; Cytarabine ; therapeutic use ; Daunorubicin ; therapeutic use ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Mercaptopurine ; therapeutic use ; Methotrexate ; therapeutic use ; Middle Aged ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Remission Induction ; Survival Rate ; Transcription Factors ; metabolism ; Vincristine ; therapeutic use ; Young Adult

OBJECTIVETo investigate the significance of detecting TCR gene clonal rearrangement in the diagnosis of mycosis fungoides (MF) and to optimize the primers used for detecting the TCR gene clonal rearrangement with PCR in paraffin embedded tissues of MF.

METHODSNineteen cases of MF were enrolled into the study. A panel of 10 antibodies were used for immunophenotypic analysis and polymerase chain reaction for TCR-γ and TCR-β gene rearrangement detection in this study.

RESULTSTCR gene clonal rearrangements were detected in all 19 cases, in which 84.2% cases (16/19) had TCR-γ gene clonal rearrangements. The positive rates of the primers T(VG)/T(JX), V(2-5)/V(8-12)/JGT(1) and BIOMED-2-TCR-γ were 47.4%, 78.9% and 31.6%, respectively. The positive rate of V(2-5)/V(8-12)/JGT(1) was statistically significantly higher than that of T(VG)/T(JX) and BIOMED-2-TCR-γ (P < 0.05). No TCR gene clonal rearrangement was detected using the primers V(γ11)/V(γ101)/Jγ12 and V(γ11)/V(γ101)/J(p12). TCR-β gene clonal rearrangement was detected in 31.6% (6/19) cases.

CONCLUSIONSTCR gene clonal rearrangement analysis is a useful tool in the diagnosis of MF and TCR-γ gene is a good target gene for the detection. The primers T(VG)/T(JX), V(2-5)/V(8-12)/JGT(1) and BIOMED-2-TCR-γ can be used in clinicopathologic detection for TCR gene clonal rearrangement and V(2-5)/V(8-12)/JGT(1) may be the first choice.

Adolescent ; Adult ; Aged ; Antigens, CD7 ; metabolism ; Base Sequence ; CD2 Antigens ; metabolism ; CD3 Complex ; metabolism ; CD4 Antigens ; metabolism ; Child ; Child, Preschool ; Female ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Humans ; Leukocyte Common Antigens ; metabolism ; Male ; Middle Aged ; Molecular Sequence Data ; Mycosis Fungoides ; diagnosis ; genetics ; metabolism ; pathology ; Paraffin Embedding ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; Skin Neoplasms ; diagnosis ; genetics ; metabolism ; pathology ; Young Adult

This study was aimed to investigate abca5, mdr-1, kdr, dapk and irf-1 expressions in leukemia stem/progenitor cells (LSC) from CD7 positive acute myeloid leukemia, the expression of these 5 genes in mononuclear cells (MNC) from 15 normal bone marrow (NBM) and 16 AML patients bone marrow (AML BM) specimen were detected by real-time quantitative PCR (RQ-PCR). CD34(+)CD38(+) progenitor cells and CD34(+)CD38(-)Lin(-) stem cells were sorted by flow cytometry (FCM) from the MNCs of 10 NBM and 21 AML BM specimen. These 5 gene expressions in the sorted cells were detected by small amount cell RQ-PCR. The results showed that these 5 genes above mentioned all expressed in NBM-MNC, in which the expression levels of irf-1 and dapk were highest with the relative expression levels 4.08 and 3.86, the expression levels of abca 5 and mdr-1 were in the middle with the relative expression 0.49 and 0.84 respectively, the kdr expression was lowest with the relative expression level 0.02. In CD34(+)CD38(+) progenitor cells, the expression level of kdr increased dramatically (p < 0.05) while irf-1 and dapk dramatically decreased (p < 0.05). There was no obvious change of expression in the rest 2 genes. In CD34(+)CD38(-) stem cells the expression level of these 5 genes all increased nearly 2 times as much as that in CD34(+)CD38(+) progenitor cells, but kdr increased 3 times as much, and the increase of kdr and irf-1 expressions was of statistical significance (p < 0.05). Compared with the NBM, expression levels of 5 genes in AML-MNC decreased, and out of them abca 5, mdr-1, kdr and dapk were decreased most remarkably (p < 0.05). Comparison between AML CD34(+)CD38(+) cells and AML MNC showed that the expression level of irf-1 and dapk were decreased dramatically (p < 0.05) while the rest 3 genes increased their expression with statistical significance (p < 0.05). The expression levels of these 5 genes were higher in CD34(+)CD38(-) cells than those in CD34(+)CD38(+) stem cells, and the increase of kdr and irf-1 expressions showed statistical difference (p < 0.05). These 5 genes expression levels were all higher than those in CD34(+)CD38(+) cells whether in AML CD34(+)CD38(-)CD7(+) cells or CD34(+)CD38(-)CD7(-) cells. The increase of kdr expression in CD34(+)CD38(-)CD7(+) cells as well as kdr and irf-1 expressions in CD34(+)CD38(-)CD7(-) cells were all of statistical significance (p < 0.05). In conclusion the expression level of kdr in NBM was highest in stem cells while dapk and irf-1 were highest in differentiated cells. The expression levels of these 5 genes in CD34(+)CD38(-)Lin(-) stem cells were higher than those in CD34(+)CD38(+) progenitor cells. The gene expressions in AML CD34(+)CD38(-)CD7(+) cells and CD34(+)CD38(-)CD7(-) cells are in accordance with the characteristics of stem cells.
Adolescent ; Adult ; Aged ; Antigens, CD7 ; immunology ; Bone Marrow Cells ; chemistry ; immunology ; Case-Control Studies ; Female ; Flow Cytometry ; Gene Expression Regulation, Leukemic ; Hematopoietic Stem Cells ; chemistry ; immunology ; Humans ; Leukemia, Myeloid, Acute ; genetics ; immunology ; Male ; Middle Aged ; Stem Cells ; chemistry ; immunology ; Young Adult

OBJECTIVETo explore the expression of CD34 in patients with acute promyelocytic leukemia (APL) and investigate the clinical and laboratory features of CD34(+) APL patients.

METHODS262 APL patients diagnosed by chromosome analysis and/or fusion gene examination in the last five years were retrospectively analyzed in this study. To survey the expression of CD34 in those patients, all the cases were divided into two groups (CD34(+) APL vs. CD34(-) APL). The clinical features including age, gender, abnormal values of the peripheral hemogram before treatment, the complete remission (CR) rate and the incidence of DIC and laboratory data such as the results of morphology, immunology, cytogenetics and molecular biology (MICM) between those two groups were compared.

RESULTSOf the 262 APL patients, 38 (14.5%) cases were positive for CD34 expression. There were no statistically significant differences between CD34(+) APL and CD34(-) APL groups in gender and age (P > 0.05). Before treatment, the median level of WBC in CD34(+) APL was 25.92 x 10(9)/L, which was significantly higher than that of CD34(-) APL (5.3 x 10(9)/L, P < 0.05). CD34(+) APL by morphology classification were mostly of the subtypes M3b and M3v (65.8%), while these subtypes in CD34(-) APL (40.3%) were significantly less (P < 0.01). There were no statistically significant differences between the two groups compared in respect of complete remission (CR) rate and the incidence of DIC (P > 0.05). The expression level of CD34 in APL had correlation to the expression level of CD2, CD7 and CD117; the latter three phenotypes in CD34(+) APL were significantly higher than those in CD34(-) APL (P < 0.01). No significant difference was found between those two groups by chromosome analysis, but there was more PML-RAR-alpha transcript short form in CD34(+) APL than that in CD34(-) APL (P < 0.05).

CONCLUSIONCD34(+) acute promyelocytic leukemia is a unique subtype of APL with different biological characteristics.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; blood ; Antigens, CD7 ; blood ; Antineoplastic Agents ; therapeutic use ; CD2 Antigens ; blood ; Child ; Disseminated Intravascular Coagulation ; etiology ; Female ; Humans ; Immunophenotyping ; Leukemia, Promyelocytic, Acute ; complications ; drug therapy ; genetics ; immunology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Phenotype ; Promyelocytic Leukemia Protein ; Proto-Oncogene Proteins c-kit ; blood ; Receptors, Retinoic Acid ; metabolism ; Remission Induction ; Retinoic Acid Receptor alpha ; Retrospective Studies ; Transcription Factors ; metabolism ; Translocation, Genetic ; Tretinoin ; therapeutic use ; Tumor Suppressor Proteins ; metabolism ; Young Adult

BACKGROUND: Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL. METHODS: From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results. RESULTS: The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NK-cells was cytoplasmic CD3+, surface CD3-, CD16/56+, CD2+, and CD5-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases. CONCLUSIONS: The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.
Adolescent ; Adult ; Aged ; Antigens, CD7/*analysis ; Blood Cell Count ; Child ; Child, Preschool ; Cytogenetics ; Female ; Herpesvirus 4, Human/isolation & purification ; Humans ; Immunophenotyping ; Karyotyping ; Leukemia, Large Granular Lymphocytic/*diagnosis ; Male ; Middle Aged ; Retrospective Studies ; Tumor Markers, Biological/*analysis

OBJECTIVETo explore the immunophenotypic characteristics of CD7 and/or CD56 positive acute myeloid leukemic stem cells, and the relationship between minimal residual disease (MRD) and the leukemic stem cells (LSC).

METHODSThe immunophenotype of leukemia cells from 51 CD34+ CD38+ CD7+ and/or CD34+ CD38+ CD56+ acute myeloid leukemia (AML) patients (exclude M3) at diagnosis was analyzed by using 4 - 6 panels of 4 color antibodies, and cells from 28 normal bone marrow (NBM) samples were served as control. The expression of CD7 and CD56 in the CD34+ CD38+ subpopulation was used as a leukemic cell marker for monitoring MRD of 53 samples from 26 CD7+ and (or) CD56+ patients.

RESULTSIn CD7+ and/or CD56+ AML patients at diagnosis, the average positivity of CD7 in CD34+ CD38+ subpopulation and CD34+ CD38- Lin- stem cells subpopulation was (77.39 +/- 20.71)% and (44.57 +/- 22.70)%, and that of CD56 was (56.71 +/- 32.56)% and (33.51 +/- 29.64)%, respectively, all significantly higher than that of NBM (P < 0.01 and P < 0.05). Compared with that of NBM, the expression of CD90 in AML patients was significantly lower in the CD34+ CD38- Lin- subpopulation (P < 0.01), the expression of CD123 was significantly higher than NBM (P < 0.01), and the expression of CD117 was no significant difference (P > 0.05). In follow up of CD7+ and (or) CD56+ patients, the expression rate of CD7 and (or) CD56 in the CD34+ CD38- Lin- subpopulation MRD+ group was significantly higher than that in the MRD- group. The actual rate for CD7 was 71% (15/21) and 16% (4/25) (P = 0.001), and its relative rate was 81% (17/ 21) and 24% (6/25) (P = 0.000), respectively. The actual rate of CD56 is 100% (4/4) and 12% (3/25) (P = 0.001), and its relative rate was 75% (3/4) and 20% (5/25) (P = 0.031), respectively. A high CD7+ CD34+ CD38- Lin- subpopulation frequency at diagnosis in CD7+ AML patients predicted a high frequency of positive MRD in later detection (P < 0.05).

CONCLUSIONSCD7 and CD56 are expressed on the stem cells in CD7+ and/or CD56+ AMLs and a high frequency of CD7 and CD56 in the CD34+ CD38- Lin- stem cell subpopulation predicts a high frequency of positive MRD in later detection.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD7 ; genetics ; CD56 Antigen ; genetics ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hematopoietic Stem Cells ; immunology ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; genetics ; immunology ; Neoplastic Stem Cells ; immunology ; Young Adult