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.

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.

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.

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.

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.

The diversity of immune repertoire (IR) is closely related to immune function and tumors derived from B or T lymphocytes.In recent years,the development of next generation sequencing has greatly promoted the progression and application of IR analysis.The research of IR has become a new hotspot of the American Society of Hematology Annual Meeting in 2016.Relevant reports in this meeting will be reviewed together with advances in research and application of IR analysis in hematological malignancies in recent years.

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.

Chimeric antigen receptor T cell (CAR-T) therapy has shown promising perspective in clinical trails of B cell hematologic malignancies.Meanwhile,this therapy still need to be further improved in the following aspects:design of CAR-T,cancer antigens selection,T cells origin,and clinical application strategy.CAR-T immunotherapy is one of hot topics in the 56th American Society of Hematology (ASH) annual meeting.Some breakthroughs have been reported in both basic research and clinical trails.

The detection of JAK2 V617F and CALR mutations,which was first reported in 2005 and 2013,respectively,had greatly improved the diagnosis and treatment of myeloproliferative neoplasms (MPN).Most MPN patients are inclined to thrombophilia,the carrier frequency of JAK2 V617F mutation was also high in patients of various thrombotic events,and the relationship between the two conditions needs further study.The observation of JAK2 V617F mutation in control group and general population also enlightened and changed the understanding about the development of chronic cancer.Research progress in this area will be introduced together with the related reports in the 56th American Society of Hematology annual meeting in 2014.