1.Research progress on microRNA related to diffuse large B-cell lymphoma
Journal of Leukemia & Lymphoma 2012;21(12):763-766
microRNA (miRNA) is a class of endogenous small non-coding RNA (20-25 nt) which can regulate the expression of protein-coding genes post-transcriptionally and participate in a series of critical biological processes including cell proliferation,differentiation,metabolism,apoptosis,et al.Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype.DLBCL is defined as the malignant lymphoma which originates from the B cells,with aggressive clinical behaviors and significant clinical heterogeneity.In recent years,the researches on miRNA in DLBCL have shown that several kinds of miRNA directly involved in the occurrence and development of tumors and there is a correlation between the miRNA expression profiles and molecular subtypes of DLBCL.As a kind of new molecular target,miRNA has a broad prospect in the application both for diagnosis and biotherapy of DLBCL.
2.Clinical significance of bcl-6, p53, c-myc aberrations in diffuse large B-cell lymphoma
Lanlan HE ; Feng YAN ; Deliang LIU ; Xiangshan CAO ; Xiaobao XIE ; Zhilin WANG
Journal of Leukemia & Lymphoma 2013;22(11):661-664
Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods Interphase fluorescence in situ hybridization (I-FISH) was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases (30.5 %),bcl-6 rearrangement in 11 cases (18.6 %),5 cases with c-myc rearrangement (8.5 %).In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones (33.3 % vs 75.6 %,x2 =9.560,P =0.002).The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant (OS,P =0.107; PFS,P =0.094),p53 deletion positive patients was in significantly worse prognosis than the negative group (OS,P =0.031; PFS,P =0.028),c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant (OS,P =0.163; PFS,P =0.167).In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant (P < 0.05).In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse (OS,P =0.003; PFS,P =0.007).Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.
3.Recent advances on associated antigens of chronic myeloid leukemia
Journal of Leukemia & Lymphoma 2012;21(12):766-768
Chronic myeloid leukemia (CML) is one of myeloid malignancies,and there is no effective treatment method at present.Nowaday,many studies report that combined treatment and adoptive immunotherapy can rebuild immunological function of patients,it's an ideal method of cure CML.So searching optimal leukemia-associated antigens and researching the number of antigen specific T lymphocytes is the key to treat CML.
4.Allogeneic hematopoietic stem cell transplantation for the treatment of chronic myeloid leukemia in blast crisis
Journal of Leukemia & Lymphoma 2013;22(6):330-335
The treatment for chronic myeloid leukemia is still a challenge,at present.Tyrosine kinase inhibitors can partially control chronic myeloid leukemia in blast crisis (CML-BC),but the effect is not durable.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way that can cure CML-BC.This paper presents a review of the treatment before allo-HSCT for CML-BC,the selection of condition regimen,donor and hematopoietic stem cell,the monitoring of MRD post-transplant,the prophylaxis and intervention of relapse.
5.Advances on gene mutations of adult acute myeloid leukemia with normal karyotypes
Journal of Leukemia & Lymphoma 2012;21(2):122-125
Acute myeloid leukemia (AML) is a disease with marked heterogeneity in both response to therapy and survival. Numerous genetic mutations which cannot be identified by cytogenetic detection have been found including gene mutations in Fms-liketyrosine kinase 3 (FLT3), nucleophosmin 1 (NPM1), and CCAAT enhancer-binding protein-α (CEBPA).Furthermore,the panel of known molecular markers is continuously increasing,for example,considering the recently described isocitrate dehydrogenase (IDH1/2) and Wilms Tumour 1 gene (WT1)mutations. This review focuses on the structures and features of these gene mutations,as well as their influence on the prognosis of AML.
6.Relationship between XPD Lys751Gln polymorphisms and the risk of adult acute leukemia
Yun XIAO ; Kun WU ; Yongmei LIU
Journal of Leukemia & Lymphoma 2010;19(10):613-615
Objective To detect the relationship between XPD Lys751Gln polymorphism and the risk of adult acute leukemia (AL). Methods 100 adult AL patients and 100 controls were chose as case and Lys751Gln were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) analysis in peripheral blood. Results The genotype frequency of Lys/Lys, Lys/Gln, Gln/Gln were 83 %, 16 %, 1% in case group and 90 %, 10 %, 0 in control group, respectively. The difference the two groups was no signficant difference (x2=1.44, P =0.49). No significantly increased risk for adult AL was observed for those carrying variant genotype with OR analysis (x2 = 2.10, P =0.15, OR =1.84; 95 % CI 0.80-4.25). Individuals with the variant genotype of XPD Lys751Gln might enhance the risk of adult AL (OR =2.77, 95 % CI 0.99-7.73). Conclusion XPD Lys751Gln polymorphism is found to have relationship with adult acute lymphocytic leukemia.
7.Changes and prognostic significance of bone marrow oil drop and megakaryocyte counts of the bone marrow in acute myeloid leukemia patients (non-M3)
Jieyu WANG ; Minghua YU ; Tao SU ; Wenyu CAI ; Tiejun QIN ; Zefeng XU ; Yue ZHANG ; Zhijian XIAO
Journal of Leukemia & Lymphoma 2011;20(12):742-746
Objective To investigate the changes and prognostic significance of bone marrow(BM) oil drop and megakaryocyte counts after chemotherapy in acute myeloid leukemia (AML) patients (non-M3).Methods Ninty-nine adult patients with denovo AML (non-M3) were retrospectively analyzed to evaluate the change of BM oil drop and megakaryocyte counts and their influences on overall survival(OS) and disease free survival (DFS) during all stages of standardized therapy.Results The median DFS and OS were 21 (2-88);months and 70 (4-89) months,respectively; and 3-year predicted DFS and OS were 47.3 % and 55.8 %,respectively.After AML patients (non-M3) achieving complete remission (CR) by induction therapy,BM oil drop tended to increase along with postremission chemotherapy cycle accumulation, while megakaryocyte counts tended to decrease.The univariate analysis indicated that megakaryocyte counts decreased after the second course of postremission therapy. BM oil drop increased after the first to the third course of postremission therapy.Grade of myelofibrosis in BM biopsy,serum lactate dehydrogenase (LDH) level at diagnosis,flow cytometric immunophenotyping, the percentage of BM blast cells at diagnosis and the percentage of residual leukemic cells (RLC) during aplasia (7-10 days after the end of induction therapy) had prognostic significance.Multivariable COX analysis indicated the percentage of BM blast cells at diagnosis and change of BM oil drop after the third postremission therapy were independent prognostic factors for DFS (P =0.010,0.018 respectively),and RLCs during aplasia and change rate of the megakaryocyte counts after the second postremission therapy were independent prognostic factors for OS (P =0.009, 0.038respectively).Conclusion After AML patients (non-M3) achieving CR by induction therapy,BM oil drop tends to increase along with postremission chemotherapy cycles accumulation,while the megakaryocyte counts tend to decrease.Dynamic observations of bone marrow oil drop and megakaryocyte counts are helpful for assessing the prognosis of acute myeloid leukemia (non-M3).
8.Expression of CD38 and ZAP-70 in chronic lymphocytic leukemia patients and their clinical significance
Xiaoyan ZHANG ; Min MAO ; Ling FU ; Yan LI ; Li AN ; Xiaomin WANG
Journal of Leukemia & Lymphoma 2012;21(9):540-542
Objective To investigate the expression of CD38 and ZAP-70 in chronic lymphocytic leukemia and the relationship between the clinical stages and prognostic significance.Methods Flow cytometry was used to analyze CD38 and ZAP-70 expression in CLL,the patients were divided into high-risk group (Ⅲ,Ⅳ stage) (25 cases) and low-medivm risk group (0,Ⅰ,Ⅱ stage) (17 cases) according to Rai clinical stages.The distribution of CD38 and ZAP-70 expression in Rai clinical stages and the prognostic significance were analyzed.Results Positive expression of CD38 was 47.6 % (20/42) in all patients,64.0 %(16/25) patients in high-risk group and 23.5 % (4/17) in low-medium risk group.The distribution of CD38 expression had significant difference between two groups (x2 =6.645,P =0.014).Positive expression of ZAP-70 was 40.5 % (17/42) in all patients,60.0 % (15/25) patients in high-risk group and 11.8 % (2/17) in low-medium risk group.The distribution of ZAP-70 expression had significant difference between two groups (x 2 =9.772,P =0.003).The patients with ZAP-70+ CD38 and ZAP-70+ CD38 were more distribute in high risk campare to the CD38+ ZAP-70- in low-medium risk group (x 2=10.076,9.346,6.005,all P < 0.05).Follow-up 48 months (1-136 months),the progression-free survival of patients with ZAP-70+ CD38+ and ZAP-70 CD38 were respectively for 19.0 and 58.0 months (x2 =11.488,P =0.003).The progression-free survival of ZAP-70+CD38 or ZAP-70 CD38+ were 43.5 and 51.7 months and not statistically significant (x2 =0.075, P =0.784).Conclusion CD38 and ZAP-70 positive expression occurs in large proportion of CLL patients with advanced stages (Rai Ⅲ and Ⅳ stage) and according to the clinical stages the expression of CD38 and ZAP-70 may be predicted.The current findings suggest that both ZAP-70 and CD38 expression should be assessed in patients with CLL for the definition of prognostic subgroups.
9.Clinicopathologic and molecular genetics features of mature aggressive B-cell lymphomas in pediatrics
Beibei Lü ; Chunju ZHOU ; Wenping YANG ; Zifen GAO ; Xuemin XUE ; Liping GONG
Journal of Leukemia & Lymphoma 2011;20(3):154-158
Objective To investigate the immunophenotype and molecular genetics of mature aggressive B-cell lymphomas in Chinese pediatric patients and provide the criteris for the diagnosis of them.Methods We collected 97 paraffin-embeded tissue samples of pediatric cases of mature aggressive B-cell lymphomas including 81 Burkitt lymphoma (BL) cases, 8 diffuse large B cell lymphoma (DLBCL) cases and 8unclassifiable B cell lymphoma with featares intermediate between BL and DLBCL (BL/DLBCL) cases. The immunophenotype and genetic features of them were detected by immunohistochemistry and interphase FISH.Results The expression of bcl-2 [3 %(2/66) in BL, 50 % (4/8) in DLBCL, 50 % (4/8) in BL/DLBCL], MUM1 [17 % (12/71) in BL, 63 % (5/8) in DLBCL, 63 % (5/8) in BL/DLBCL] and mean Ki-67 proliferation index [(93±4.4)% in BL, (83±14.3)% in DLBCL, (80±11.5)% in BL/DLBCL] were significantly different between BL and DLBCL and between BL and BL/DLBCL. The frequency of c-myc rearrangement [98 % (79/81) in BL,38 % (3/8) in DLBCL, 50 % (4/8) in BL/DLBCL] and an extra copy of bcl-6 [0 % in BL, 38 % (3/8) in DLBCL, 25 % (2/8) in BL/DLBCL] were also significantly different between BL and DLBCL and between BL and BL/DLBCL. Conclusion Diagnosis of the mature aggressive B cell lymphomas in pediatrics should be based on the comprehensive review and integration of morphologic, immunohistochemical and molecular genetic features. BL/DLBCL is more likely a subgroup of the DLBCL in pediatric population. The expression of CD10 and bcl-6 but not bcl-2, a high Ki-67 PI (>90 %) and a c-myc rearrangement but not bcl-2 or bcl-6rearrangement are the features of BL. Regardless of the expression of CD10 and bcl-6, positive staining for bcl2, Ki-67 PI below 90 % and an extra copy of the bcl-6 favor a diagnosis of DLBCL or BL/DLBCL.
10.MUM1/IRF4 expression in follicular lymphoma and its clinical and pathological significance
Shuangmei ZOU ; Jianming YING ; Liyan XUE ; Shan ZHENG ; Xiuyun LIU ; Peng WEN ; Ning Lü
Journal of Leukemia & Lymphoma 2011;20(6):353-356
Objective To clarify the MUM1/IRF4 expression in follicular lymphoma (FL) and its clinical and pathological significance. Methods Ninety-six cases FL were immunostained with MUM1,CD10,bcl-2,bcl-6 and Ki-67 antibodies. The results were compared with their clinical and pathological features. Results The overall MUM1 expression rate in FL was 59.2 % (58/96),including 36.2 % (19/51) grade 1 or 2 and 86.4 %(39/45) grade 3 cases (x2 =24.406,P <0.001). 68.9 % cases with diffuse area were MUM1 positive (x2 =8.161,P =0.004). MUM 1 and CD10 expression had inverse correlation,83.3 % CD10 negative cases were MUM1 positive (x2= 12.649,P<0.001). The mitosis rate and Ki-67 label index were statistically higher in MUM1 positive cases than in negative cases (t = -3.852 & -4.610,respectively,P <0.001). Conclusion MUM1 can be used as a biomarker to divide FL into different malignancies. The MUM1 positive FL may be the feature of high grade non germinal center B cell malignant lymphoma.