1.Prognosis and related factors of acute lymphoblastic leukemia.
Wei ZHANG ; Rong FU ; Wen-Hui LIU ; Yu-Qian CHENG ; Wen-Xiu SONG ; Li-Juan DU ; Er-Bao RUAN ; Li-Tong ZHANG ; Xiao-Ming WANG ; Yong LIANG ; Guo-Jin WANG ; Wen QU ; Jia SONG ; Rong-Li ZHANG ; Jing GUAN ; Li-Juan LI ; Peng ZOU ; Zong-Hong SHAO
Journal of Experimental Hematology 2007;15(5):1102-1106
In order to analyze the prognosis and related factors of acute lymphoblastic leukemia (ALL), 53 newly diagnosed ALL patients were enrolled in this study. The therapeutic efficacy and prognosis of 53 cases of ALL were analyzed, the remission, relapse, overall survival and event-free survival were studied, and relation between different factors and prognosis of ALL were investigated by comparison of cases in same stage. The results showed that the complete remission was achieved in 36 out of 53 patients, the total remission rate was 67.9%, the total relapse rate was 37.7%, the median relapse duration was 6 months after remission. Median overall survival (OS) and median event-free survival (EFS) time were 4 and 1 months after remission respectively, OS and EFS rate of 18 month was 35.1% and 14.2%. The patients with different gender had significantly different EFS. Age was an independent risk factor of CR rate. White blood cell count and hemoglobin level of newly diagnosed patients were significantly correlated with OS and EFS. Absolute neutrophil count (ANC) at the end of the induction chemotherapy was an independent related factor of OS, the higher ANC, the lower risk of death. The patients with or without chemotherapy related infection had different relapse rate. The patients with bleeding after chemotherapy had lower OS when compared with those without bleeding. Serum glucose level was a significant negative prognostic factor. It is concluded that there is higher relapse rate, poor prognosis in adult ALL in comparison with children. In order to decrease the relapse rate and prolong the EFS, individual therapeutical regimens and prophylaxis of complicating diseases should be applied to ALL patients.
Adolescent
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols
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therapeutic use
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Child
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Female
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Humans
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Male
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Middle Aged
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Neoplasm Recurrence, Local
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prevention & control
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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diagnosis
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therapy
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Prognosis
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Young Adult
2.Study on the dendritic cell subsets in peripheral blood and its relationship with the expressions of T-bet and GATA-3 in lymphocytes in severe aplastic anemia.
Jun WANG ; Zong-hong SHAO ; Rong FU ; Er-bao RUAN ; Wen QU ; Yong LIANG ; Hong LIU ; Yu-hong WU ; Jia SONG ; Hua-quan WANG ; Li-min XING ; Jing GUAN ; Li-juan LI ; Hui LIU ; Shu-wen DONG ; Li YOU ; Peng ZOU
Chinese Journal of Hematology 2008;29(11):733-736
OBJECTIVETo investigate the relationship between the dendritic cell (DC) subsets and transcriptive factors, T-bet, GATA-3, and immune imbalance in acquired severe aplastic anemia (SAA).
METHODSThe DC1 (HLA-DR+Lin-CD11c+) and DC2 (HLA-DR+Lin-CD123+) in peripheral blood mononuclear cells (PBMNC) were measured with flow cytometry (FCM), the expressions of T-bet mRNA and GATA-3 mRNA in PBMNC with semiquantitative RT-PCR and the plasma level of IFN gamma and IL-4 with ELISA in 29 SAA patients and 16 healthy controls.
RESULTSThe percentages of DC1 in PBMNC were (0.44 +/- 0.24)% and (0.73 +/- 0.30)% in untreated and recovered SAA patients respectively, both were higher than that in controls (0.29 +/- 0.10)% (P < 0.05). The percentage of DC2 in the untreated cases was lower than that of recovered ones or controls [(0.18 +/- 0.14)% vs (0.28 +/- 0.20)% and (0.29 +/- 0.13)%] (P < 0.05). DC1/DC2 ratios were 3.45 +/- 2.71 and 2.90 +/- 0.95 in untreated and recovered groups respectively, both were higher than that in controls (1.15 +/- 0.56) (P < 0.05). No statistic difference in DC1/DC2 ratio was found between untreated and recovered patients (P < 0.05). The relative mRNA expression levels of transcriptive factor T-bet were 0.37 +/- 0.07, 0.20 +/- 0.07 and 0.17 +/- 0.05 in the above 3 groups, respectively, untreated group being higher than that of recovered group or healthy controls (P < 0.05). There was no statistic difference of GATA-3 expression among the 3 groups (P > 0.05). T-bet/GATA-3 ratio was 0.72 +/- 0.13 in untreated group, being higher than that of recovered group (0.33 +/- 0.08) or controls (0.35 +/- 0.11). The plasma level of IFN gamma in the untreated group was (50.9 +/- 1.1) ng/L, which was higher than that of recovered group [(49.7 +/- 0.9) ng/L] or controls [(49.7 +/- 0.7) ng/L]. There was significant positive correlations between T-bet and DC1/DC2 ratio (r = 0.445, P < 0.01), as well as between T-bet and IFN gamma (r = 0.402, P < 0.01).
CONCLUSIONEither DC1/DC2 or T-bet/GATA-3 ratio might become an index to estimate immune imbalance. High-expressed T-bet was related to the progress of SAA. In patients with SAA, DC1/DC2 ratio returns to normal range later than that of routine blood test does, indicating that immunosuppressive therapy should not be withdrawn too earlier.
Adolescent ; Adult ; Anemia, Aplastic ; blood ; immunology ; Child ; Dendritic Cells ; immunology ; Female ; GATA3 Transcription Factor ; blood ; genetics ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Middle Aged ; RNA, Messenger ; genetics ; T-Box Domain Proteins ; blood ; genetics ; Young Adult
3.Quantity and subtypes of dendritic cells in patients with immune related pancytopenia and their clinical significance.
Guang-Shuai TENG ; Rong FU ; Hui LIU ; Hong-Lei WANG ; Yi-Hao WANG ; Er-Bao RUAN ; Wen QÜ ; Yong LIANG ; Guo-Jin WANG ; Xiao-Ming WANG ; Hong LIU ; Yu-Hong WU ; Jia SONG ; Hua-Quan WANG ; Li-Min XING ; Jing GUAN ; Jun WANG ; Li-Juan LI ; Zong-Hong SHAO
Journal of Experimental Hematology 2012;20(3):722-726
This study was aimed to investigate the quantity and subtypes of dendritic cells (DC) in patients with immune related pancytopenia (IRP) and to explore the role of DC in pathogenesis of IRP. The quantity of plasmacytoid dendritic cells (pDC, Lin(-)HLA-DR(+) CD123(+) cells) and myeloid dendritic cells (mDC, Lin(-)HLA-DR(+) CD11c(+)cells) in peripheral blood of 65 patients with IRP (37 new diagnosed and 28 remitted) and 17 healthy controls were analyzed by flow cytometry. The results indicated that the ratio of pDC in peripheral blood mononuclear cells (PBMNC) was (0.91 ± 064)% in new diagnosed group, which was significantly higher than that in remission group (0.39 ± 0.11)% and control group (0.29 ± 0.13)% (P < 0.01), while this ratio of pDC in remission group was higher than that in control group (P < 0.05). The ratio of mDC in PBMNC was (0.21 ± 0.20)% in new diagnosed group and (0.34 ± 0.21)% in remission group respectively, there was no statistical difference as compared with control group (0.29 ± 0.09)% (P > 0.05). The ratio of pDC to mDC in new diagnosed group was 6.75 ± 7.11, which was significantly higher than that in remission group (1.55 ± 0.93) and control group (1.07 ± 0.43, P < 0.01), there was no statistical difference between the ratio of remission group and control group (P > 0.05). The ratio of pDC in PBMNC of IRP group negatively correlated to ratio of Th1/Th2 (r = -0.347, P < 0.05), and positively correlated to the ratio of auto-antibody on membrane of BMMNC (r = 0.606, P < 0.05) and to the quantity of CD5(+)B cells (r = 0.709, P < 0.05), while it negatively correlated to the levels of hemoglobin (r = -0.381, P < 0.01) and platelets (r = -0.343, P < 0.01). The ratio of mDC in PBMNC positively correlated to the ratio of Th1/Th2 (r = 0.595, P < 0.05) and the level of hemoglobin (r = 0.292, P < 0.05). The ratio of pDC/mDC negatively correlated to ratio of Th1/Th2 (r = -0.395, P < 0.05), it positively correlated to the level of antibody on membrane of BMMNC (r = 0.421, P < 0.05) and the quantity of CD5(+)B cells (r = 0.423, P < 0.05), while it negatively correlated to the levels of hemoglobin (r = -0.304, P < 0.05) and platelets (r = -0.287, P < 0.05). It is concluded that the quantity of pDC in peripheral blood of IRP patients increases, which may be related to the immunopathogenesis of IRP.
Adolescent
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Adult
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Blood Cell Count
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Case-Control Studies
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Child
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Child, Preschool
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Dendritic Cells
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cytology
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immunology
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Female
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Flow Cytometry
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Humans
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Male
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Middle Aged
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Pancytopenia
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blood
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immunology
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Young Adult
4.Application of bone marrow indirect Coombs test and its clinical significance in diagnosis of immuno-related pancytopenia.
Li-Juan BING ; Rong FU ; Hui LIU ; Hong-Lei WANG ; Er-Bao RUAN ; Wen QU ; Yong LIANG ; Guo-Jin WANG ; Xiao-Ming WNAG ; Hong LIU ; Yu-Hong WU ; Jia SONG ; Hua-Quan WANG ; Li-Min XING ; Li-Juan LI ; Zong-Hong SHAO
Journal of Experimental Hematology 2012;20(2):505-509
This study was purposed to applicate the bone marrow indirect Coombs test and investigate its clinical significancies in diagnosis of immuno-related pancytopenia (IRP). 30 patients with pancytopenia including 22 cases of IRP and 8 cases of idiopathic cytopenia of undetermined significance (ICUS), and 15 patients with iron-deficiency anemia as controls were enrolled in this study. After incubation of the bone marrow supernatant of IRP patients and bone marrow nucleated cell (BMNC) of controls was used as experiment group, while the incubation of BMNC and bone marrow supernatant of controls was used as control group. After incubation for 45 min, the positive rate of membrane antibodies in bone marrow hematopoietic cells (CD15(+), GlyCoA(+) and CD34(+)cells) was detected by flow cytometry, and correlation analysis of positive rate with clinical data of patients were analyzed. The results showed that among 30 patients with pancytopenia (16 positive and 14 negative for bone marrow direct Coombs test) 16 cases showed positive for bone marrow indirect Coombs test, with positive rate 53.33. In the experiment group, the median positive rate of CD15(+)IgM was 0.34, which was significantly higher than that in control group (0.20, P < 0.05); the median positive rates of CD34(+) IgG and IgM were 0.64 and 0.21 respectively, which were significantly higher than those in control group (0.00, P < 0.05) and (0.00, P < 0.05); the positive rates of GlyCoA(+)IgG and IgM were (0.83 ± 0.75) and (2.12 ± 1.98) respectively, which were significantly higher than those in control group [(0.47 ± 0.43), P < 0.05, (0.68 ± 0.64), P < 0.01]; the positive rates of CD15(+) IgG and IgM were positively correlated with the ratio of CD5(+)B cells. The positive rates of GlyCoA(+) IgG and IgM negatively correlated with the Hb level, percentage of reticulocytes, the ratio of bone marrow erythroid lineage and DC1/DC2 positively correlated with the ratio of CD5(+)B cells and indirect bilirubin level. It is concluded that antibodies (IgG or IgM) aiming at the bone marrow hematopoietic cells exist in the supernatant of some IRP and ICUS patients, and may act on the membrane protein of the normal BMNC. These antibodies correlate with the prognosis of IRP.
Adolescent
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Adult
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Aged
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Bone Marrow Cells
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immunology
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Child
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Coombs Test
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Female
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Humans
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Male
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Middle Aged
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Pancytopenia
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diagnosis
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immunology
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Young Adult
5.Preliminary study on the quantity and function of T follicular helper cells in the cytopenic patients with positive BMMNC-Coombs test.
Hong YU ; Rong FU ; Yi-hao WANG ; Hua-quan WANG ; Hui LIU ; Li-juan LI ; Hong-lei WANG ; Er-bao RUAN ; Wen QU ; Xiao-ming WANG ; Guo-jin WANG ; Yu-hong WU ; Hong LIU ; Jia SONG ; Li-Min XING ; Jing GUAN ; Zong-hong SHAO
Chinese Journal of Hematology 2013;34(7):606-609
OBJECTIVETo study the quantity and function of bone marrow (BM) T follicular helper (Tfh) cells of the cytopenia patients with positive bone marrow mononuclear cells (BMMNC)- Coombs test (also known as immuno-related pancytopenia, IRP), and explore the role of Tfh cells in the pathogenesis of IRP.
METHODSForty- three untreated IRP patients, 47 recovered IRP patients and 25 healthy donors were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 and Bcl-6 in BM were investigated by flow cytometry and semiquantitive RT-PCR.
RESULTSThe ratio of CD4⁺CXCR5⁺/CD4⁺ cells of untreated IRP patients [(28.79 ± 19.70)%] was significantly higher than that of recovered IRP patients [(21.15 ± 12.81)% ] and normal controls ([ 13.42 ± 6.72)% ](P<0.05). The ratio of CD4⁺CXCR5⁺ICOS⁺/CD4⁺CXCR5⁺ cells of untreated IRP patients [(5.05 ± 4.71)% ] was significantly higher than that of recovered IRP patients [(2.96 ± 2.89)% ] and normal controls [(2.99 ± 2.23)% ] (P<0.05). The ratio of CD4⁺CXCR5⁺CD40L⁺/CD4⁺CXCR5⁺ cells of untreated IRP patients [(5.87 ± 4.14)%] and recovered IRP patients [(6.52±5.47)%] were significantly higher than that of normal controls [(2.93 ± 2.92)%] (P<0.05). The ratio of intracytoplasmic CD4⁺CXCR5⁺IL-21⁺/CD4⁺CXCR5⁺ cells of untreated IRP patients [(8.20 ± 7.41)% ] and recovered IRP patients [(6.30 ± 6.03)% ] were significantly higher than that of normal controls [(3.43 ± 3.40)%] (P<0.05). The relative expressions of Bcl-6 mRNA in BMMNC were 0.625 ± 0.248, 0.485 ± 0.253, 0.306 ± 0.210 in three groups, respectively. The differences between untreated IRP patients, recovered IRP patients and normal controls were significant (P<0.05).
CONCLUSIONThere exists increased quantity and hyperfunction of Tfh cells in the IRP patients, they may play important role in the pathogenesis of IRP. Tfh cells and their related effector molecules could be a potential therapeutic target for the disease.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Child ; Child, Preschool ; Coombs Test ; Female ; Flow Cytometry ; Humans ; Interleukins ; metabolism ; Lymphocyte Count ; Male ; Middle Aged ; Pancytopenia ; blood ; diagnosis ; etiology ; T-Lymphocytes, Helper-Inducer ; cytology ; metabolism ; Young Adult
6.Expressions of miR-21, miR-155 and miR-210 in plasma of patients with lymphoma and its clinical significance.
Tian-Tian GE ; Yong LIANG ; Rong FU ; Guo-Jin WANG ; Er-Bao RUAN ; Wen QU ; Xiao-Ming WANG ; Hong LIU ; Yu-Hong WU ; Jia SONG ; Hua-Quan WANG ; Li-Min XING ; Jing GUAN ; Li-Juan LI ; Zong-Hong SHAO
Journal of Experimental Hematology 2012;20(2):305-309
This study was purposed to investigate the expressions of miR-21, miR-155 and miR-210 in plasma of patients with lymphoma, and explore their role played in diagnosis, evaluation of chemotherapy effect and prognosis of lymphoma. The expressions of miR-21, miR-155 and miR-210 were assayed by RT-PCR in plasma of 54 cases of lymphoma, 10 cases of lymphonode inflammation and 27 cases of normal controls. The results indicated that the expressions of miR-21, miR-155 and miR-210 in plasma of lymphoma patients were higher than those of control group and lymphonode inflammation group (P < 0.05). The expressions of miR-21 and miR-210 in plasma of control group and lymphonode inflammation group had no significant differences (P > 0.05). The expression of miR-21 in plasma of lymphoma patient group significantly correlated with their serum LDH level. The expressions of miR-21 and miR-210 in plasma of previously untreated lymphoma patient group were higher than those of the patients treated for 6 or more courses (P < 0.05). The diagnostic accuracy of miR-21, miR-155 and miR-210 used for lymphoma patients was 56, 65, 48 respectively, and reached to 83 when combined three of them. It is concluded that the expressions of miR-21, miR-155 and miR-210 in plasma of lymphoma patients were significantly higher. Detection of these 3 miRNA in plasma of patients can contribute to the clinical diagnosis, treatment and prognosis evaluation of lymphoma.
Adult
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Aged
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Aged, 80 and over
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Case-Control Studies
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Female
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Humans
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Lymphoma
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blood
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diagnosis
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Male
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MicroRNAs
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blood
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Middle Aged
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Plasma
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metabolism
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Prognosis
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Young Adult
7.Clinical analysis of 102 blood disease patients with gram positive cocci infection treated with Linezolid.
Jing GUAN ; Rong FU ; Er-Bao RUAN ; Yong LIANG ; Wen QU ; Guo-Jin WANG ; Xiao-Ming WANG ; Hong LIU ; Yu-Hong WU ; Jia SONG ; Hua-Quan WANG ; Li-Min XING ; Zong-Hong SHAO
Chinese Journal of Hematology 2010;31(8):527-530
OBJECTIVETo observe the efficacy and safety of linezolid for the treatment of gram positive coccus infections in hematological disease patients.
METHODSOne hundred and two hematological disease patients with suspected or proven gram positive coccus bacteria infection were enrolled in this study. Linezolid was given at a dosage of 600 mg, iv, q12h. The mean treatment period was (10.82 ± 5.12) days (1 to 51 days) with 74.5% over 7 d and 51.0% over 10 d.
RESULTSAmong 102 patients, 57 were male, 45 female aged 11 to 81 years, with a mean of (45.26 ± 19.15) years. Ninety four cases were nosocomial infection (92.2%) and 8 community infection (7.8%); There were pneumonia in 80 (78.4%), septicemia in 11 (10.8%), and infection of other organsin 11 (10.8%); Forty five cases were proven gram positive coccus bacteria infection, and 57 were suspected infection; Fifty one bacteria strains were isolated from cultivated samples of proven patients, in which 22 were staphylococcus aureus with 19 methicillin resistant 13 hemolytic streptococcus, 9 staphylococcus epidermidis with 7 methicillin resistant 6 enterococcus faecom, and 1 enterococcus hirae. Seven cases were mixed with one kind gram negative bacillus infection, 4 mixed with two kinds of gram negative bacillus infection, and 12 mixed with fungal infection; Total clinical response rates by ITT (intention to treatment) analysis was 69.6%, in which 40 (39.2%) were curative and 31 (30.4%) obviously effective; PP (per-protocol) analysis was 70.9%, in which 39 (41.9%) were curative and 27 (29.0%) obviously effective. Bacteria clearance rate was 70.6%, and in this group the clinical effective rate was 88.9%; Adverse effect rate was 2.9%, being transient thrombocytopenia and increased transaminase.
CONCLUSIONLinezolid is a safe and effective antibiotic used in hematological disease patients complicated with infections of gram positive coccus.
Acetamides ; Anti-Bacterial Agents ; therapeutic use ; Cross Infection ; microbiology ; Gram-Positive Bacterial Infections ; drug therapy ; Gram-Positive Cocci ; Hematologic Diseases ; drug therapy ; Humans ; Linezolid ; Oxazolidinones ; Staphylococcus aureus
8.STAT5 phosphorylation in CD34(+)CD38(-)CD123(+) bone marrow cells of the patients with myelodysplastic syndrome.
Bing-nan LIU ; Rong FU ; Hua-quan WANG ; Li-juan LI ; Lan-zhu YUE ; Er-bao RUAN ; Wen QU ; Yong LIANG ; Guo-jin WANG ; Xiao-ming WANG ; Hong LIU ; Yu-hong WU ; Jia SONG ; Li-min XING ; Jing GUAN ; Jun WANG ; Zong-hong SHAO
Chinese Journal of Hematology 2012;33(6):480-483
OBJECTIVETo investigate the expressions of STAT5 phosphorylation in CD34(+)CD38(-)CD123(+) bone marrow cells of the patients with myelodysplastic syndromes (MDS), and then evaluate the level of activation of STAT5 associated with cell proliferation in MDS clone cells.
METHODSThe bone marrow mononuclear cells (BMMNC) were extracted from 36 MDS patients and 14 normal controls. The mean fluorescence intensities (MFI) of phosphorylated STAT5(P-STAT5) in CD34(+)CD38(-)CD123(+) and CD34(+)CD38(-)CD123(-)cells, with or without the stimulation of 10 U/ml EPO, were examined by flow cytometry (FCM).
RESULTSWithout stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 113.71 ± 67.22/173.05 ± 102.78, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (58.84 ± 27.51/68.99 ± 50.42, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (63.06 ± 21.06, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; With the EPO stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 144.04 ± 58.11/239.45 ± 152.05, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (68.41 ± 25, 10/64.21 ± 23.43, P < 0.01) and the normal controls CD34(+)CD38(-)CD123(-) cells (75.21 ± 27.02, P < 0.01), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; The P-STAT5 MFI in the CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients with or without EPO stimulation were 21.80/28.86, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (7.42/5.50, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (6.39, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal controls CD34(+)CD38(-)CD123(-) cells; There was no significant difference of P-STAT5 MFI with or without EPO stimulation and the increased P-STAT5 MFI between the CD34(+)CD38(-)CD123(+) cells of low and high risk MDS.
CONCLUSIONSTAT5 associated with cell proliferation was activated in CD34(+)CD38(-)CD123(+) bone marrow cells in MDS, which had more significant reactions to EPO than CD34(+)CD38(-)CD123(-) cells, indicating that CD34(+)CD38(-)CD123(+) bone marrow cells might be the real malignant MDS clone cells in MDS.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Bone Marrow Cells ; cytology ; metabolism ; Cell Proliferation ; Cells, Cultured ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; pathology ; Phosphorylation ; STAT5 Transcription Factor ; metabolism
9.Expression and clinical significance of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma.
Yi-ran ZHAO ; Rong FU ; Jing GUAN ; Shan GAO ; Hui LIU ; Er-bao RUAN ; Wen QU ; Yong LIANG ; Guo-jin WANG ; Xiao-ming WANG ; Hong LIU ; Yu-hong WU ; Jia SONG ; Hua-quan WANG ; Li-min XING ; Jun WANG ; Li-juan LI ; Zong-hong SHAO
Chinese Journal of Hematology 2012;33(4):274-277
OBJECTIVETo investigate the expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma (MM), and explore the importance of Notch signaling pathway in the formation and progression of MM.
METHODSThirty three MM patients and 15 healthy controls were enrolled in this study. The expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) and CD38(+)CD138(-) plasma cells were analyzed by flow cytometry. The clinical data of MM patients were also analyzed.
RESULTSThe ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was (60.21 ± 25.06)% which was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients (39.84 ± 18.94)% (P = 0.000) and controls (38.34 ± 19.39)% (P = 0.004). There was no statistical difference between the two latter groups (P > 0.05). The expression of Notch1 on CD38(+)CD138(+)plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there bone marrow (r = 0.914, P = 0.000), serum level of lactate dehydrogenase (LDH) (r = 0.754, P = 0.007), and β(2)-MG(r = 0.716, P = 0.013). The ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients who had renal dysfunction was correlated to their abnormal serum creatinine levels. The expression of Notch1 on CD38(+)CD138(+) plasma cells from 17 MM patients who received VD (bortezamib and dexamethasone) chemotherapy was correlated to the ratio of plasma cell reduction after the first VD chemotherapy (r = 0.842, P = 0.000).
CONCLUSIONThe expression of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients and controls. Notch1 overexpressed plasma cells were sensitive to the early VD therapy, and correlated to the progression and long term outcome of MM.
ADP-ribosyl Cyclase 1 ; immunology ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; metabolism ; Case-Control Studies ; Cell Count ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; metabolism ; Plasma Cells ; immunology ; metabolism ; Prognosis ; Receptor, Notch1 ; metabolism ; Syndecan-1 ; immunology
10.The mechanisms underlying bone marrow damage by iron overload in pancytopenic patients with positive BMMNC-Coombs test.
Lei HUANG ; Rong FU ; Li-juan LI ; Hui LIU ; Yi-hao WANG ; Hong-lei WANG ; Tian ZHANG ; Kai DING ; Shao-xue DING ; Er-bao RUAN ; Wen QU ; Jing GUAN ; Guo-jin WANG ; Jia SONG ; Hua-quan WANG ; Yu-hong WU ; Li-min XING ; Hong LIU ; Xiao-ming WANG ; Zong-hong SHAO
Chinese Journal of Hematology 2013;34(5):430-434
OBJECTIVETo investigate the mechanisms underlying bone marrow damage by iron overload in pancytopenic patients with positive BMMNC-Coombs test (IRP).
METHODSTwenty-one iron overloading, 26 non-iron overloading IRP patients and 10 normal controls were enrolled in this study. The expressions of ROS, Bcl-2, Caspase-3 and apoptosis of BMMNC were analyzed by flow cytometry (FCM). Antioxidants were added to iron overloading IRP BMMNC, and then the changes of indices above were detected by FCM. The number and apoptosis of T lymphocytes of IRP patients were also detected.
RESULTSROS and apoptosis of BMMNC, myelocytes, erythrocytes and stem cells of iron overloading IRP patients were significantly higher than that of non-iron overloading IRP ones and normal controls (P < 0.05). The expressions of Bcl-2 on BMMNC, erythrocytes and stem cells of iron overloading IRP patients were significantly lower than those of non-iron overloading IRP ones (P < 0.05). The levels of Caspase-3 on myelocytes, erythrocytes and stem cells of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP ones and normal controls (P < 0.05). After treatment with antioxidants, the expressions of ROS, Caspase-3 and apoptosis of iron overloading IRP BMMNC significantly decreased, but opposite for Bcl-2. The percentages of CD4(+) lymphocytes [ ( 40.86 ± 8.74)%] and CD4(+)/CD8(+) (1.44 ± 0.36) in PB of iron overloading IRP patients were significantly higher than that of non-iron overloading IRP ones [(35.96 ± 7.03)% and 1.14 ± 0.37] and normal controls [(28.00 ± 6.73)% and 0.79 ± 0.21], respectively (P < 0.05), as opposite for CD8(+) lymphocytes (P < 0.05). The apoptosis of CD8(+) lymphocytes [(27.35 ± 10.76)%] and the ratio of CD8(+) apoptosis/CD4(+) apoptosis (2.51 ± 0.81) in BM of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP ones [(15.47 ± 8.99)%] and normal controls (1.39 ± 0.47), respectively (P < 0.05). The apoptosis of erythrocytes and stem cells coated with auto-antibodies in BM of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP and normal controls.
CONCLUSIONMechanisms underlying bone marrow damage by iron overload might be through the follows: ①The increased ROS induced by excessive iron deposition affected the expressions of Caspase-3 and Bcl-2, which caused more BMMNC apoptosis; ②The abnormal number and ratio of T lymphocytes caused by iron overload aggravated the abnormality of immunity of IRP; ③Iron overload may increase the damage to erythrocytes and stem cells coated with auto-antibodies.
Adolescent ; Adult ; Aged ; Bone Marrow ; pathology ; Case-Control Studies ; Caspase 3 ; metabolism ; Coombs Test ; Female ; Humans ; Iron Overload ; Male ; Middle Aged ; Pancytopenia ; immunology ; pathology ; physiopathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Reactive Oxygen Species ; metabolism ; Young Adult