Allee effect is a phenomenon in ecology characterized by a correlation between population size or density and the mean individual fitness of population or species.It is consistent with density dependent phenomenon in biomedical field.Recently,Allee effect has been studied by theoretical biologist in detail for oncology biological research.Leukemia cells,which reside in organic microenvironment,show an obvious Allee effect.The authors compared Allee effect with density dependent growth of leukemia cells based on their work experience and literature data.No principle distinction was found between these two terms.In this paper,Allee effect in leukemia cell culture and leukemia,especially in minimal residual disease,will be discussed in the view of ecology.The association between Allee effect and leukemogenesis and relapse dynamics will also be explored in the future research.

Objective To explore the characteristics of chromosome karyotypes in patients with chronic myeloid leukemia (CML),and to provide help to individualized treatment.Methods The date of chromosome karyotypes of 313 patients and FISH of 45 of these patients with CML excluding Ph chromosome negative (Ph-) after treatment were collected from January 2014 to June 2015.Karyotypes were detected by R-banding.Results In the 313 cases,307 cases (98.08 ％) were Ph chromosome positive (Ph+) and 6 cases (1.92 ％) were Ph-.In the Ph+ patients,288 cases (93.81％) were classical Ph+,and 19 cases (6.19 ％) were variant rearrangements.There were 48 cases (15.34 ％) with additional chromosome changes in all patients,including 41 cases (13.10 ％) with classical Ph+ and 7 cases (2.24 ％) with variant rearrangements.The most common additional chromosome changes were in the following order:+der(22) Ph (35.42 ％),+8 (33.33 ％) and +21 (12.50 ％).The most frequent pattern of combination was +der(22) combined with +8 (16.67 ％),followed by +8 combined with +21 (10.42 ％).The proportion of pure Ph+ patients in chronic phase was higher than that of advanced phase,but proportion of classical Ph+ patients with additional chromosome changes in chronic phase was lower than that in advanced phase (x2 =1 11.55,P ＜ 0.01).The proportions of chronic phase and advanced phase patients with simple variant rearrangements were not different from those with complex variant rearrangements (P =0.582).The results of FISH in 45 cases were all positive,including 5 cases with 2 GIR1Y.Conclusion Karyotype analysis can reveal the instability of genetic and the characteristics of disease progression by identifying the evolution of Ph,which provides the basis for clinical doctors to choose suitable treatment.

Objective To explore the feasibility of low-dose chemotherapy (LDCT) combined with tyrosine kinase inhibitor (TKI) (LDCT+TKI regimen) as the first-line induction regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL).Methods The efficacies and adverse effects of various induction regimens in 61 newly diagnosed patients with Ph+ ALL were retrospectively analyzed.Results The complete remission (CR) rate of the first induction therapy was 73.8 ％ (45/61) for all 61 cases,and that of the second induction therapy was 86.7 ％ (13/15) for non-remission (NR) patients after the first induction.The total CR rate for two-course induction was 95.1％ (58/61).Treatment related mortality happened in one case (1.6 ％) after the first induction therapy.The response rates between conventional-dose chemotherapy (CDCT)±TKI group and LDCT±TKI group were not statistically different [without TKI,65.5 ％ (19/29) vs 60.0 ％(3/5),P =0.812;with TKI,90.5 ％ (19/21) vs 100.0 ％ (6/6),P =0.432].The response rate of LDCT+TKI group was not statistically different from that of CDCT alone group (P =0.089).The introduction of TKI to LDCT and CDCT could improve the response rate (CDCT+TKI group,P =0.041;LDCT+TKI group,P =0.087).The total response rate of the induction therapy with TKI was significantly higher than that without TKI [92.6 ％ (25/27) vs 64.7 ％ (22/34),P =0.01].The response rate of the TKI-based second induction therapy for non-CR cases after the first induction therapy without TKI was significantly higher than that after the first induction therapy with TKI [100.0 ％ (8/8) vs 33.3 ％ (1/3),P =0.011].There were no significant differences in the efficacies of the first induction therapy between various genetic subgroups (all P ＞ 0.05),and the introduction of TKI to the treatment of various genetic subgroups could improve the efficacies to a certain extent without statistical significance (all P ＞ 0.05).The incidences of treatment related infections and bleeding due to the first induction therapy in all patients were 50.8 ％ (31/61) and 4.9 ％ (3/61),respectively.Compared with LDCT±TKI group,the overall incidences of treatment related infections and bleeding in CDCT±TKI group were higher,but there were no statistical significances [infection,56.0 ％ (28/50) vs 27.3 ％ (3/11),P =0.084;bleeding,6.0 ％ (5/30) vs 0 (0/1 1),P =0.405].The incidence of treatment related infections in LDCT+TKI group was significantly lower than that in CDCT+TKI group [0 (0/6) vs 71.4 ％ (15/21),P =0.002] or that in CDCT alone group [0 (0/6) vs 44.8 ％ (13/29),P =0.039].The incidence of bleeding in LDCT+TKI group was not statistically different from that in CDCT+TKI group or that in CDCT alone group (all P ＞ 0.05).Conclusion LDCT+TKI regimen as the first-line induction regimen in Ph+-ALL is deserved to be investigated further.

Objective To evaluate the efficacy and safety of Chansu injection (CHS) combined with EOAP regimen in patients with advanced non-Hodgkin lymphoma (NHL).Methods 65 patients with advanced NHL were divided into two groups according to random number table.All were given EOAP regimen (VP16 60 mg/m2 on d 1-5;VCR 1.4 mg/m2 on d1;Ara-C 60 mg/m2,Q12 h,on d 1-5;Pred 60 mg/m2 on d 1-5),and the observation group received EOAP combined with CHS (20 ml/d,intravenous drip,on d 1-14).The regimen was repeated every 21 days.The efficacy and toxicity were evaluated after two cycles.Results The effective rate of the observation group was higher than that of the control group,but there was no significant difference between two groups [87.9 ％ (29/33) vs 81.3 ％ (26/32),P ＞ 0.05].The quality of life of the observation group was superior to that of the control group,and there was significant difference (P ＜ 0.05).Hematological toxicities and gastrointestinal tract reaction were the main side effects in both groups.The incidence of myelosuppression of the observation group was significantly lower than that of the control group (P ＜ 0.05).Conclusion Chansu injection combined with EOAP regimen can enhance the efficacy,reduce toxicity and improve the quality of life in the treatment of advanced NHL.

Multiple myeloma (MM) is a malignant plasma cell disease which occured predominantly in the elderly.In recent years,due to the application of small molecular proteasome inhibitor and immunomodulator,MM has become a chronic disease with good response to new treatments rather than a deadly disease that is lack of effective treatments.However,the occurrence of drug resistance makes MM less likely to be cured,which is one of the biggest challenges in MM clinical treatment.This article will review the mechanisms of acquired resistance to bortezomib in MM,including target genes modification,bypass signaling and so forth.

In recent years,the application of haploidentical stem cell transplantation makes it possible for every transplant candidate to have a donor.Therefore,choosing best donor and dealing with transplantrelated complications,such as promoting engraftment,decreasing graft-versus-host disease and relapse,become key issues to improve transplant outcomes.The advances in allogeneic hematopoietic stem cell transplantation will be reviewed.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder of hematopoietic stem cells due to acquisition of somatic mutations.Somatic mutations in phosphatidylinositol glycan class A (PIGA) account for intravascular hemolysis and other PNH manifestations,but the pathophysiology of clonal expansion of PNH cells cannot be elucidated clearly.PNH is closely related to aplastic anemia and myelodysplastic syndromes.Today,the gold standard for PNH is flow cytometry to detect the absence or severe deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on white and red blood cells.However,PNH diagnosed by phenotype is a group of heterogeneous disease in pathogenesis.Eculizumab,a first-in-class monoclonal antibody that inhibits terminal complement,is highly effective in stopping intravascular hemolysis and improving quality of life.Further research on the pathogenesis of PNH would be helpful to understand the underlying reasons for PNH phenotype cells in different patients,improve differential diagnosis and more targeted and specific therapy.Research progress in recent years will be reviewed in this article.

There are some major changes win the revised 2016 WHO Classification of Lymphoid Neoplasms.Based on the clinicopathological changes and genetic/molecular findings in the past years,the new classification clarified the diagnosis and clinical management of some very early stages of lymphoproliferative disorders,refined the diagnostic criteria for some lymphoid neoplasms,and further emphasized the significance of genetic/molecular studies in the diagnosis and clinical treatment of lymphomas.A small number of new provisional entities were added to the 2016 edition.

Objective To detect the expressions of c-myc,Bmi-1,serum insulin-like growth factor-Ⅰ (IGF-Ⅰ) and insulin-like growth factor binding protein-3 (IGFBP-3) in diffuse large B-cell lymphoma (DLBCL),and to analyze their relations with clinical stages,efficacy and prognosis.Methods 102 cases of incipient patients with DLBCL and 60 patients or health examination volunteers were chosen as DLBCL group and control group,respectively.Immunohistochemical method was used to detect expressions of c-myc and Bmi-1 in DLBCL wax samples.Chemiluminescence immunoassay method was used to determine the levels of serum IGF-Ⅰ and serum IGFBP-3.The expression differences of these factors between DLBCL group and control group and their relations with pathological types,clinical stage,IPI and chemotherapy were analyzed.Results The positive rates of c-myc and Bmi-1 were 71.6 ％ (73/102) and 61.8 ％(64/102) in the tissues of DLBCL,respectively.The positive rates of c-myc and Bmi-1 in non-GCB group were higher than those in GCB group [c-myc:80.0 ％ (48/60) vs 59.5 ％ (25/42);Bmi-1:71.7 ％ (43/60) vs 50.0 ％ (21/42)].With the increase of IPI score,the expressions of c-myc and Bmi-1 were enhanced,but there were no statistical differences between Ⅲ-Ⅳ group and Ⅰ-Ⅱ group (P ＞ 0.01).The differences of 3-year progression free survival (PFS) rate and 3-year overall survival (OS) rate between c-myc gene or Bmi-1 gene normal and abnormal had statistical significance,and 3-year PFS rate and 3-year OS rate of double-hit of c-myc gene and Bmi-1 were lower.C-myc gene and Bmi-1 gene aberrant were the independent prognosis factors.The levels of serum IGF-Ⅰ and serum IGFBP-3 in DLBCL group were significantly lower than those in the control group (P ＜ 0.01),however,the levels were increased after chemotherapy (P ＜ 0.01).Serum IGF-Ⅰ and serum IGFBP-3 levels had no significant differences between non-GCB group and GCB group (P ＞ 0.01).Their levels in stage Ⅳ group or high risk group were significantly lower than those in other groups.Serum IGF-Ⅰ level and serum IGFBP-3 level had no significant differences between the c-myc gene or Bmi-1 gene abnormal group and normal group (P ＞ 0.01),but their levels were lower in both c-myc gene and Bmi-1 gene abnormal group than those in normal group.Conclusions C-myc and Bmi-1 are related with the biological characteristics and prognosis of DLBCL.Serum IGF-Ⅰ level and serum IGFBP-3 level reflect clinical stages of DLBCL and the efficacy in a certain degree.The expressions of c-myc and Bmi-1 have some correlation with the levels of serum IGF-Ⅰ and IGFBP-3 in DLBCL.

Objective To analyze the distribution of multiple myeloma (MM) literature in Chinese periodicals and to find out the core periodicals about MM.Methods Periodical literature that involved with MM in the article titles from January 2008 to December 2014 on the Wanfang medical database was collected and searched.Bibliometric method was used to analyze journal date and journal distribution.Results 456categories of periodicals had published literature about MM.The number of articles about MM published in the top 10 journals was more than 30,accounting for 27.00 ％ of all published MM literature,which were highly effective core journals.The number of articles about MM published in the top 3 journals was more than 100,accounting for 15.59 ％ of all published MM literature.The number in Journal of Leukemia & Lymphoma had reached 187,accounting for 6.43 ％ of the total.Conclusions The core journals about MM provide the key approach to help MM medical personnel to select useful information efficiently.Furthermore,the core journals are not only the significant gist for authors who plan to contribute their articles to relevant MM periodicals,but also the necessary reference tools for medicine workers who engage in basic and clinical research and teaching.