With the progress of medical research,more and more inherited and congenital factors predisposing to hematologic malignancies have been revealed,which have brewed into a hot topic of the 56th American Society of Hematology (ASH) annual meeting in 2014.Correctly understanding and interpreting these innate susceptible factors will be of great significance in improving the treatment in patients and prevention or early detecting of cancers in individuals carrying these factors.Research progress in this area will be introduced together with the authors' research in this article.

The event free survival and overall survival rate of acute lymphoblastic leukemia (ALL)have been improved significantly based on the risk stratify diagnosis and treatment.But there are still some patients suffering therapeutic failure and relapse.With the great development of genome sequencing technology,more and more genetic aberrations behind the refractory and relapse ALL have been identified.Ph-like ALL is charactered with gene expression profile similar to that of BCR-ABL1 positive ALL,involving abnormal activation of cytokine receptor and tyrosine kinase.It has been proved that treatment combined with Tyrosine kinase inhibitors (TKIs) can significantly improve the poor prognosis.Ph-like ALL is one of hot topics during the 56th American Society of Hematology (ASH) annual meeting in 2014.Progression in molecular genetics for Ph-like ALL will be introduced together with the author' s research experience.

Telomere and telomerase play important roles in protecting and maintaining the stability and integrity of chromosomes. Telomere and telomerase are closely related with multiple diseases, and their relationship with aging and tumors has become a hot topic in recent years. Relevant reports in the American Society of Hematology Annual Meeting in 2016 will be reviewed together with advances of telomere and telomerase in hematological diseases.

Objective To develop a HPLC-MS/MS method for determination of Tacrolimus(FK506) in bone marrow trans plant patient,and explore the relationship of HPLC-MS/MS with CMIA and Elecsys in the measurement of FK506 blood drug concentration,and provide reliable basis for clinical rational use of monitoring method in FK506 blood drug concentra tion.Methods The separation was performed on a Ultimate xB-C18 column with a mobile phase of water (containing 2 mmol/L ammonium acetate and 0.1 ml/dl formic acid) and methanol (containing 0.1 ml/dl formic acid).The way of eluting was gradient.Mass spectrum detection method was ESI positive ion mode and the MRM transitions of FK506 m/z 821.5～ 768.5 and Ascomycin m/z 809.4～756.4.Selected part of the whole blood samples of FK506 in bone marrow transplant patient and respectively were tested by HPLC/MS/MS method,CMIA method and Elecsys method.Then,three methods for the detection of FK506 density were compared.Results The standard curve of FK506 was linear over the range of 0.5～50 ng/ml,Y=0.228X-0.003 08 (r=0.999 0).FK506 blood concentrations were not significantly different in HPLC/MS/MS method,CMIA method and Elecsys method.Conclusion The HPLC-MS/MS method in the detection of FK506 was established and can be used for monitoring of whole blood concentration of FK506 in bone marrow transplant patients.

Although tyrosine kinase inhibitors (TKI) have profoundly improved prognosis of patients with chronic myeloid leukemia (CML), it still can not cure CML with high relapse rate when TKI is used alone. Except for effective development of TKI and precise application of the existing TKI,the exploitation of new therapy target, research on treatment for leukemia stem cells and cocktail targeted therapies also provide further inspiration for improving treatment and curing CML. This article will introduce the advances of therapy in CML.

BACKGROUND:Implantation of bone morphogenetic protein (BMP) or vascular endothelial growth factor (VEGF) alone, without support vectors, is easy to be flushed away by the blood flow, and thus limits the osteogenesis and angiogenesis.
OBJECTIVE: To observe the effects of combination of calcium phosphate cement (CPC), BMP-6/VEGF in bone defect repair.
METHODS:Defect models of the bilateral medial femoral condyle were prepared in New Zealand white rabbits. Then, the medial femoral condyle was filed with CPC/BMP-6/VEGF, CPC/BMP-6, and CPC, respectively, in the left side, but nothing in the right side as control. After 8 and 16 weeks of implantation, the hard tissue slices were prepared for histological observation and scanning electron microscope observation.
RESULTS AND CONCLUSION:Al three kinds of materials showed good biocompatibility, and no obvious inflammation was found. After 8 weeks of implantation, the junction of the CPC/BMP-6/VEGF and bone tissue was almost completely covered by newly formed trabecular bone. With the development of cement degradation, abundant osteoblasts could be found in the surface of newborn trabecular bone. After 16 weeks of implantation, an ongoing cement degradation and bone formation was seen. Moreover, newly formed bone tissue increased and became thicker. The cement in the interface was separated into smal pieces and closely interconnected with the surrounding tissues, and newly formed bone showed a mesh-like ingrowth into the cement. This newly formed bone was mature and could not be distinguished from the original trabecular bone. Both the degradation and osteogenesis of CPC and CPC/BMP-6 were much slower than that of CPC/BMP-6/VEGF (P < 0.05). This study demonstrates angiogenesis and osteogenesis in vivo through the additive effects of VEGF and BMP-6. CPC/BMP-6/VEGF can be an ideal bone substitute in bone repair.

BACKGROUND:The transplanted tendon must have good biomechanical properties, in order to effectively avoid tendon tear at the anastomosis end during suturing and reduce adhesion of tendon during healing process. OBJECTIVE:To investigate the effects of different methods for preparation of graft materials on the biological properties of tendon al ograft. METHODS:Forty-eight healthy male Leghorns were randomly divided into three groups:vitrification group, chemical extraction group, and control group. Unilateral superficial and deep flexor tendon of the third toe was subjected to vitrification, chemical extraction and no treatment in the three groups, respectively. A part of tendon was taken for biomechanical testing, and the other part was for al ogeneic transplantation. After 1, 2, 3, 6 weeks, peripheral blood CD4+, CD8+T lymphocytes were counted. RESULTS AND CONCLUSION:Vitrification could partial y retain the original tendon cells, but the chemical extraction method could not. Tensile strength for tendon rupture, tensile fracture power and tensile elongation at break were not statistical y significant among three groups (P>0.05). At the end of 1 and 2 weeks after transplantation, CD4+, CD8+, CD4+/CD8+difference was significant among the three groups (P<0.05);at the end of 3 and 6 weeks after transplantation, CD4+, CD8+, CD4+/CD8+were significantly less in the vitrification and chemical extraction groups than the control group (P<0.05), but no difference was found between the vitrification group and chemical extraction group (P>0.05). These findings indicate that the vitrification and chemical extraction methods can significantly reduce immunogenicity of the tendon based on effective retention of biomechanical properties of the tendon.

Objective To evaluate the sickness impact and the quality of life in patients who received 131 I treatment for Grave's disease with one year of follow-up.Methods 376 patients with Grave's disease(GD) who voluntarily received 131I treatment were recruited.The follow-up archives were established.The Sickness Impact and the Quality of life in patient' s with GD were measured using the Sickness Impact Profile (SIP),Self-Rating Anxiety Scale (SAS),Self-Rating Depression Scale(SAS) and Social Disability Screening Schedule (SDSS) and Quality of life scale(QLS,SF-36) before and after treatment with 131I for 6 months and 12 months.Results 57 out of 376 cases were lost.319 cases finished follow-up studies.There was significant difference of SAS,SDS,SDSS,SIP and SF-36 and their agent score among three groups:before and 6months and 12months after 131I treatment in the 319 patients(F=8.561-1080.317,P＜0.001).After treatment with 131I,SAS,SDS,SDSS and SIP score were lower(P＜0.05),SF-36 total and agent score were higher(P＜0.05).There was no significant difference between the score of SAS,SDS,SDSS,SIP total score and it' s agent score of SD-Ⅱ,SR,W,SF-36 agent score of RP,BP,VT,SF at the end of 12 months compared to the score at the end of 6 months(P＞0.05).But there was significant difference between the score of SIP agent score of SD-Ⅰ,HM,RP,SF-36 total score and it' s agent score of PF,GH,RE,M H at the end of 12 months compared to the score at the end of 6 months (P＜0.05).At the end of 6 months and 12 months after treatment the subjects were divided five groups according to different clinical outcome.Not only at the end of 6 months,but also at the end of 12 months,there was significant difference of SAS,SDS,SDSS,SIP total score,and it' s agent score of SD-Ⅰ,SD-Ⅱ,SR,W,RP,SF-36 total score,and it's agent score PF,RP,BP,GH,VT,SF,RE,MH among the five groups(F6 =6.870-143.790,F12 =13.956-837.184,P＜0.001).There was no significant difference of HM among five groups (F6 =1.733,P6 =0.142; F12 =2.015,P12 =0.092).The score of SF-36 and its agent score PF,RP,VT,SF,RE,MH in three subgroup (healthy control,the patient group at end of 6 months and 12 months with normal thyroid function) was significant different,respectively(F=8.320-82.791,P＜0.001).There was no significant different for agent score of BP and GH(F=2.990,2.652,P=0.051,0.072).Conclusion Quality of life of patients with GD is decrease.131I treatment can improve it,but socialpsycho function can not be improved satisfactorily.It is necessary for GD patients to pay attention to the quality of life and provide effective mental intervention to improve the recovery completely.

Objective To develop a HPLC-MS/MS methodfor determination of cyclosporin A(CSA)and AM1 in bone marrow transplant patient,and explore the relationship of CSA and its main metabolite AM1 within individual and between individuals,and provide reliable basis for clinical rational use of monitoring in CSA blood drug concentration.Methods CSD was used as internal standard,and whole blood samples were treated with internal standard methanol precipitated protein.The column was Ultimate XB-C18 with a column temperature of 65 ℃ and the mobile phase was eluted with 0.1％ of formic acid and 2 mmol/L ammonium acetate in water and methanol containing 0.1％ formic acid.The mass spectrometry was detected by electrospray ion trap positive ion mode,MRM scanning,monitoring CSA 1219.9 to 1203.1 m/z,AM1 1236.1 to 1219.1 m/z,CSD 1234.0 to 1217.0 m/z.Results The concentration of CSA was linear in the range of 16 to 1600 ng/mL,Y=0.0143X+0.0213(r=0.9976).The concentration of AM1 was linear in the range of 10～1000 ng/mL,Y=0.00363X-0.00528(r=0.9973).The ratio of CSA to AM1 (AM1/CSA) between individual ranged from 32％ to 356％.The ratio of CSA to AM1 within indiviolual(AM1/CSA) ranged from 27 ％ to 147 ％.Conclusion HPLC-MS/MS method for the simultaneous detection of CSA and AM1 was established.The variation of CSA exists in the bone marrow transplant patient between individuals and within individual;the HPLC-MS/MS method can be used for monitoring of whole blood concentration of CSA in bone marrow transplant patients.

The efficacy of hematological tumor drugs has shown inter-patient variability. Pharmacogenomics focuses on gene polymorphisms of drug metabolizing enzymes, drug transporters and therapeutic targets and its impact on pharmacokinetics (PK)/pharmacodynamics (PD). Initial dose and adverse reaction can be predicted based on inherited gene polymorphisms, and therapeutic drug monitoring (TDM) also helps to adjust drug dosage in the course of treatment. Thus can achieve rational drug use and personalized medicine, and improve the efficacy and reduce the incidence of adverse drug reactions. This article will introduce the relevant research progress in recent years, and the concept of personalized medication fingerprints is proposed.