Analysis of ASXL1 gene variant in patients with myelodysplastic syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect ASXL1 gene variants among patients with myelodysplastic syndrome (MDS) and explore their correlation with variants of other genes and clinical features of patients.@*METHODS@#For 149 patients with MDS, genomic DNA was amplified by PCR and subject to direct sequencing to identify variants of ASXL1, U2AF1, SF3B1, DNMT3A, TET2, IDH1/2, NPM1, FLT3-ITD and C-KIT genes.@*RESULTS@#ASXL1 variants were found among 37 patients (24.8%). Other commonly mutated genes included U2AF1 (22.8%), TET2 (11.4%), DNMT3A (9.4%), NPM1 (8.1%) and SF3B1 (6.0%). The frequency of concurrent U2AF1 and TET2 variants among patients with ASXL1 variants was slightly higher than that of wild-type patients. No significant difference was found in median age, MDS subtype, karyotype, peripheral leukocytes, hemoglobin, platelet levels, and bone marrow blast counts between the ASXL1-variant and the wild-type groups (P> 0.05). Twenty-nine patients harboring ASXL1 variants were followed up, 37.9% progressed to acute myeloid leukemia (AML). The rate of transformation in ASXL1-variant group was significantly higher than the wild-type group (37.9% vs. 14.1%, P< 0.01).@*CONCLUSION@#ASXL1 showed a high frequency of variant among MDS patients, which was frequently accompanied with U2AF1 and TET2 variants. Compared with the wild type group, patients with ASXL1 variants were more likely to progress to AML.

Molecular genomic landscape of myeloid neoplasms in elderly patients / 中华老年医学杂志

Objective:To explore the molecular genetics of myeloid neoplasms in elderly patients.Methods:High-throughput DNA sequencing was performed to detect 49 target gene mutations in 26 patients with acute myeloid leukemia(AML)and 51 patients with myelodysplastic syndrome(MDS). Genomic DNA-PCR and Sanger sequencing were used to detect the mutations of CALR gene exon 9, NMP1 gene exon 12, FLT3-ITD and the two functional domains, TAD and BZIP, in CEBPA.Results:(1)Of the 77 patients enrolled, the overall incidence of gene mutations was 91.0%(71/77), with an average of 2 mutations per patient and an incidence of 42.9% for the coexistence of 3 or more gene mutations(33/77), and the most common genetic mutations were NPM1, U2AF1, RUNX1, TET2, ASXL1, TP53, DNMT3A, IDH2, BCOR, and FLT3-ITD, and the incidence of other genetic mutations was<10%.(2)The incidence of double gene mutations in the AML group was significantly higher than that in the MDS group, and the incidence of≥3 gene mutations in the MDS group was higher than that in the AML group( P<0.05). The AML group was associated with significantly higher incidences of NPM1, FLT3-ITD, and CEBPA double mutations and lower incidences of BCOR and ASXL1 mutations than those in the MDS group(all P<0.05). Functional classification showed that tyrosine kinase receptor gene mutations mainly occurred in the AML group( P=0.004), while chromatin modified gene mutations mainly occurred in the MDS group( P=0.007). (3)Fifty-one cases with MDS were followed up and 9 cases developed leukemia transformation with an average transformation time of 6.5 months during the period, and the conversion rate of patients with RUNX1 and U2AF1 mutations was 44.4%, which was higher than that of other gene mutations. Conclusions:Elderly patients with myeloid neoplasms have unique gene mutation profiles.The types and frequencies of common myeloid tumor gene mutations are different in AML and MDS, and some gene mutations in patients with MDS are related to leukemia transformation.

Characteristics of a patient with myeloid neoplasm and co-existence of t(7;11)(p15;p15) and t(5;12)(q33;p13) translocations / 中华医学遗传学杂志

OBJECTIVE@#To delineate the clinical and molecular characteristics of a patient with myeloid neoplasm and co-existence of t(7;11)(p15;p15) and t(5;12)(q33;p13) translocations.@*METHODS@#Clinical data of the patient was collected. Conventional karyotyping, reverse transcriptase (RT)-PCR and next generation sequencing (NGS) were carried out to delineate its genetic features.@*RESULTS@#The patient has featured recurrent rash, fatigue, loss of appetite and splenomegaly. Laboratory test suggested hyperleukocytosis of FAB-M2-subtype. Neither eosinophilia nor basophilia was presented. NUP98/HOXA9 and ETV6/PDGFRB fusion genes were detected by RT-PCR. NGS and DNA-PCR showed the co-existence of WT1 p.C423Y, KRAS p.G12D and DNMT3A p.R882C mutations. The patient achieved morphological remission after imatinib plus coventional chemotherapy (standard IAC regimen). However, the disease has relapsed shortly after. Treatment was switched to HHT-Ara-C-Acla regimen, no hematological response was observed. The ETV6/PDGFRB fusion gene was undetectable in bone marrow sample, though strong expression of NUP98/HOXA9 was detectable throughout the whole course.@*CONCLUSION@#Acute myeloid leukemia in association with the co-existence of NUP98/HOXA9 and ETV6/PDGFRB fusion genes have unique clinical and genetic features. Imatinib seems to have no impact on the overall survival in such cases.

Characterization of mutational pattern of patients with core-binding factor acute myeloid leukemia / 中华医学遗传学杂志

OBJECTIVE@#To characterize the mutational profile of patients with core-binding factor acute myeloid leukemia (CBF-AML).@*METHODS@#A total of 81 acute myeloid leukemia patients were recruited, which included 36 cases of CBF-AML and 45 cases of cytogenetically normal acute myeloid leukemia (CN-AML) . Mutations of FLT3-ITD, FLT3-TKD, NPM1, c-KIT, NRAS, KRAS, TET2, IDH1/2, RUNX1, DNMT3A, GATA2, ASjXL1, TP53, PTPN11, JAK2V617F, SETBP1 and CEBPA genes were simultaneously detected by DNA-based PCR and Sanger sequencing.@*RESULTS@#Over all, mutations were detected in 68 patients (83.9%), with the most common ones including double CEBPA mutations (n=17), followed by NPM1 (n=15), c-KIT (n=11), NRAS (n=10), TET2 (n=9), FLT3-TKD (n=9), FLT3-ITD (n=8), IDH1 (n=7), RUNX1 (n=7), KRAS (n=7), DNMT3A (n=6), IDH2 (n=4), and GATA2 (n=4) mutations. AML1-ETO and CBFβ-MYH11 fusions were present in 21 and 15 patients, respectively. Coexistence of ≥2 mutations was more common in CN-AML comparing with CBF-AML. The mutation rate of NPM1, FLT3-ITD, DNMT3A, IDH1 and CEBPA double mutations were higher in patients with CN-AML. NRAS, c-KIT and KRAS mutations were identified more frequently in patients with CBF-AML (P<0.05). Based on the function, aberration of genes involved in DNA methylation, NPM1 proteins and transcription predominated in CN-AML, while tyrosine kinase receptor signaling and RAS pathways have predominated in CBF-AML.@*CONCLUSION@#The genomic landscape of CBF-AML patients has differed from that of CN-AML patients. Synergy of fusion genes with particular mutations may impact the clinical phenotype and prognosis of patients.

Effect of PI3K/mTOR Signal Pathway Inhibitor XL765 on Human Leukemic KG-1 Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the effect and possible mechanism of PI3K/mTOR inhibitor XL765 on KG-1 cells in vitro.@*METHODS@#The effect of XL765 on cell proliferation was detected by CCK-8 assay. The colony formation test (200 cells were plated in a plate for 9 days) was used to detect the effect of XL765 on the colony forming ability of KG-1 cells. The apoptosis was assessed by flow cytometry with Annexin V-FITC/PI double staining. Quantitative real-time polymerase chain reaction (q-PCR) was used to detect the expression of cell apoptosis-related genes BCL-2, BAX and caspase-3, Western blot was performed to detect the expression levels of BCL-2, BAX, Caspase-3, and the phosphorylation change of p-PI3K, p-AKT and p-S6K.@*RESULTS@#XL765 effectively inhibited the proliferation and the colony formation of KG-1 cells (P=0.0002). XL765 (150 nmol/L) induced KG-1 cell apoptosis (31.87±1.376%), very statistically significant different from (3.533±0.4179% ) in the control group (P＜0.01). Treatment with 150 nmol/L XL765 could in a significantly increase the expression levels of BAX and active caspase-3, and decreases expression level of the BCL-2 (P＜0.01). In accordance with these results, the Western blot further confirmed the expression decrease of BCL-2 protein along with the increase BAX and cleaved caspase-3 activity. XL765 statistically significantly down-regulated the phosphorylation levels of PI3K, AKT and S6K.@*CONCLUSION@#PI3K/mTOR inhibitor XL765 substantially suppresses KG-1 cell proliferation and induces apoptosis by inhibiting the activation of PI3K-AKT-mTOR signaling pathway, and regulating the apoptosis-related proteins.

Mutation analysis of 77 patients with normal-karyotype myelodysplastic syndrome / 中华医学遗传学杂志

Objective@#To carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype.@*Methods@#Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing.@*Results@#Sixty two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation.@*Conclusion@#Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.

Mutation analysis of 77 patients with normal-karyotype myelodysplastic syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype.@*METHODS@#Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing.@*RESULTS@#Sixty-two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation.@*CONCLUSION@#Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.

Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells / 中华血液学杂志

Objective@#To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro.@*Methods@#Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1.@*Results@#BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression.@*Conclusion@#Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.

Different types of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: therapeutic efficacy and safety / 中国组织工程研究

BACKGROUND: With the optimization of transplantation scheme and the emergence of graft-versus-host disease (GVHD) therapy drugs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recent years has made great progress that makes patients with hematological malignancies have more long-term survival opportunities. OBJECTIVE: To compare the efficiency and safety of three types of allo-HSCT used in the treatment of adults with Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (Ph+ALL).METHODS: A total of 69 patients with Ph+ALL who received allo-HSCT from June 2006 to November 2013 were enrolled, including 23 cases of sib-matched donor transplantation, 24 cases of unrelated-matched donor transplantation, and 22 cases of haploidentical donor transplantation. There were 54 cases of CR1, 13 cases of CR2 to CR3 and 3 cases of relapse. The bone marrow or/and peripheral blood stem cells were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan, cyclophosphamide and total body irradiation. GVHD was prevented by combined use of immunosuppressants including cyclosporine A, short-term methotrexate, mycophenolate mofetil and anti-human thymocyte globulin, etc.RESULTS AND CONCLUSION: The results showed that 68 patients acquired hematopoietic reconstitution, and only 1 case of haploidentical donor transplantation failed. The mean follow-up period was 20.4 months. The acute GVHD incidence of the sibling matched-HSCT, unrelated donor HSCT and related haploidentical allo-HSCT was 30％, 33％ and 45％,respectively; the chronic GVHD incidence (cGVHD) incidence was 22％, 29％ and 36％, respectively; the incidence of aGVHD and cGVHD between groups showed no statistically significant difference. Transplant related mortality (TRM) was 9％, 29％ and 41％, respectively, and there was a significant difference among groups (0.01 < P < 0.05). Recurrence rates were 17％, 21％ and 14％, respectively, and there was no significant difference among groups. The 3-year overall survival rates were 68％, 49％ and 43％, respectively; there were significant differences between sib-matched-HSCT and the other two groups, but no statistically significant difference was found between unrelated donor HSCT and related haploidentical allo-HSCT groups. The 3-year overall survival rate was 58％ for 54 patients in CR1 and 41％ for 15 patients in non-CR1 states. To conclude, the sib-matched HSCT has better effect than unrelated donor transplantation and related haploidentical allo-HSCT; Ph+ALL patients should do transplantation as early as possible in the state of CR1.

Differentiation of K562 Cells Induced by Pulsatilla Saponin A into Erythroid Lineage / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the differentiation-inducing potentiality of Pulsatilla saponin A on K562 cells.</p><p><b>METHODS</b>Pulsatilla saponin A of different concentrations was used to treat K562 cells; the benzidine staining and the hemoglobinometry were applied to measure the change of hemoglobin content; the flow cytometry (FCM) was used to detect the expression of CD71 and GPA on K562 cells.</p><p><b>RESULTS</b>K562 cells treated with 4 µg/ml pulsatilla saponin A differentiated into the erythroid lineage. With the treatment of pulsatilla saponin A, the hemoglobin content in K562 cells increased significantly; CD71 and GPA expression on the K562 cell surface were up-regulated.</p><p><b>CONCLUSION</b>Pulsatilla saponin A can induce K562 cells to differentiate into erythroid lineage.</p>

Effects of Simvastatin on Expression of Multidrug Resistance Gene and Protein of SHI-1 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin(SIM) and serum free medium(SFM) on the expression of multidrug resistance gene(MDR1) and protein of SHI-1 cells.</p><p><b>METHODS</b>Trypan blue exclusion assay was used to detect the proliferation level and viability of SHI-1 cells after treatment with SIM and culture in SFM; The multi-drug resistant protein p-gp was measured by flow cytometry after culture in SFM for 1 to 3 days and treatment with various concentration of simvastatin. The effect of SFM culture and SIM treatment on the expression of MDR1 trascript was detected by qPCR; ELISA was used to measure the change of cellular cholesterol after culture in SIM and SFM. Chemosensitivity assay was performed after treatment with SIM for SHI-1 cells.</p><p><b>RESULTS</b>Compared with control group, the growth of SHI-1 cells cultured in SFM decreased in a time-dependent manner. The growth-inhibitory effect was markedly increased when SHI-1 cells were treated with SIM and SFM. The mRNA level of MDR1 gene decreased after SIM treatment or/and culture in SFM. P-gp protein was downregulated in SHI-1 cells cultured in SFM or/and treated with SIM. The cellular cholesterol level increased when the cells were cultured in SFM. Total cellular cholesterol level decreased in SHI-1 cells treated with SIM and cultured in SFM. Chemosensitivity assays found that pre-treatment with SIM could increase the cytotoxicity of DNR to SHI-1 cells.</p><p><b>CONCLUSION</b>Culture with SIM and SFM can downregulate the expression of MDR1 gene and p-gp protein in SHI-1 cells. SIM also can enhance the chemotherapeutic sensitivity of SHI-1 cells.</p>

Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of T Cell Lymphoblastic Lymphoma - Clinical observation of 10 Cases / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the result of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of patients with T cell Lymphoblastic lymphoma(T-LBL).</p><p><b>METHODS</b>The engraftment, graft versus host disease (GVHD), infection, relapse and survival of 10 T-LBL patients received allo-HSCT was observed. The clinical outcome of allo-HSCT for T-LBL patients was analyzed.</p><p><b>RESULTS</b>The median age of patients was 25 years old, 10 (6 males and 4 females) T-LBL patients received allo-HSCT including 3 from HLA-matched unrelated donors, 3 from HLA-matched sibling donors, 2 from HLA haploidentical sibling donors, and 2 from haploidentical related donors. The clinical staging showed that 1 case was in stage III and 8 cases were in stage IV. The bone marrow was involved in 7 patients. All the 10 patients achieved engraftment, and the median times of neutrophil and platelet engraftment were 11 (10-19) days and 12(7-19) days, respectively. Acute GVHD occurred in 5 patients and chronic GVHD occured in 1 patient. After the median follow-up of 26 months (11-51 months), 3 patients died, out of them 1 died from relapse after transplantation, 1 from infection and 1 from GVHD. The relapse, overall survival, and disease-free survival rate were 10%, 70%, 70%,respectively. And the estimated overall survival rate was 66.7%.</p><p><b>CONCLUSION</b>T-LBL has high rate of relapse and poor prognosis. The allo-HSCT can improve the survival of patients with T-LBL, and is an effective method for treatment of T-LBL patients.</p>

Study of molecular mechanism and antigen expression of CisAB01 blood group / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of CisAB01 subtype in the ABO blood group system, and to investigate the expression of A and B antigens in red blood cells (RBCs).</p><p><b>METHODS</b>For 5 unrelated individuals with the CisAB phenotype, the molecular basis for the blood type was studied with serological assay, DNA sequencing and haplotype analysis. Bioinformatics analysis was carried out to investigate the changes in structure and function of relevant enzymes. Expression of A and B antigens in RBCs of CisAB01 was detected by flow cytometry.</p><p><b>RESULTS</b>All of the 5 samples were found to have a CisAB01 subtype. The underlying mutations, 467C>T and 803G>C in exon 7, have resulted in replacement of amino acid P156L and G268A. The mean fluorescence intensity (MFI) of A antigen in CisAB01 cases was 135, while the control group was 172. The B antigens in CisAB01 cases (MFI=38) showed significant decrease in MFI compared with the control group (MFI=164).</p><p><b>CONCLUSION</b>803G>C mutation of the ABO gene probably underlies the CisAB01 subtype. Fluorescence intensity of A antigens in CisAB01 subtype cases is slightly lower than the normal type, while the B antigen was significantly lower.</p>

8p11 myeloproliferative syndrome with CEP110-FGFR1 fusion in a patient / 中华医学遗传学杂志

OBJECTIVE To explore the clinical and laboratory features of a patient with 8p11 myeloproliferative syndrome (EMS) and CEP110-FGFR1 fusion. METHODS Combined bone marrow cytology, fluorescence in situ hybridization, fusion gene detection was used to analyze the patient. RESULTS Clinically, the patient had many features similar to those with chronic myelomonocytic leukemia, which included hyperleukocytosis, marked eosinophilia, monocytosis, myeloid hyperplasia and hyperplasia. Fluorescence in situ hybridization analysis for FGFR1 gene rearrangement was positive. Further study of the mRNA also confirmed an in-frame fusion between exon 38 of the CEP110 gene and exon 9 of FGFR1 gene. CONCLUSION EMS with CEP110-FGFR1 fusion is a very rare and distinct myeloproliferative neoplasm. FISH and molecular studies may improve its diagnosis.

Clinical and gene involved of one case of 8p11 myeloproliferative syndrome with ins(13;8)(q12;p11p23) / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the understanding of patients with 8p11 myeloproliferative syndrome (EMS) harboring ins(13;8)(q12;p11p23)/ZNF198 -FGFR1.</p><p><b>METHODS</b>We reported here a 8p11 EMS case and provided more details on the clinical and molecular features of ins(13;8)(q12;p11p23)/ZNF198-FGFR1，full length ZNF198-FGFR1 was cloned by overlap extension PCR method，and the literatures on this topic were reviewed.</p><p><b>RESULTS</b>Clinically, the case with ins(13;8)(q12;p11p23)/ZNF198-FGFR1 had distinct hematological and clinical characteristics: hyperleukocytosis, myeloid hyperplasia，widespread adenopathy and lymphoma; Fluorescence in situ hybridization (FISH) disclosed the positive FGFR1 gene rearrangement; Further molecular studies confirmed a mRNA in-frame fusion between exon 17 of the ZNF198 gene and exon 9 of FGFR1 gene ，the full length ZNF198-FGFR1 was composed of a NH2 terminus of ZNF198 including the ZNF and proline-rich domains, whereas the COOH terminus of FGFR1 included 2 tyrosine kinase domains.</p><p><b>CONCLUSION</b>EMS with ins(13;8)(q12;p11p23)/ZNF198 -FGFR1 was a very rare， distinct myeloproliferative neoplasm, the fusion gene and chimeric protein with constitutive activation of the FGFR1 tyrosine kinase.</p>

Clinical Analysis on Treatment of Chronic Myelomonocytic Leukemia with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze retrospectively the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).</p><p><b>METHODS</b>The engraftment, graft versus host disease (GVHD), infection, relapse, and survival of 13 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.</p><p><b>RESULTS</b>Thirteen (10 males and 3 females) CMML patients with a median age of 38 years old received allo-HSCT including 4 from HLA-matched unrelated donors, 6 from HLA-matched sibling donors and 3 from haploidentical related donors. All 13 patients achieved engraftment, and the median time of neutrophil engraftment and platelet engraftment were 12 (11-18) days and 15 (10-55) days respectively, acute GVHD occurred in 8 patients. After the median follow-up of 13 (6-29) months, the overall survival, disease free survival and relapse were 53.8%, 53.8%, 7.7%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT can improve the survival of patients with CMML, and is a effective method for treatment of CMML.</p>

Relation between alternatively spliced tissue factor and tumor / 国际肿瘤学杂志

Serine/ aginine rich(SR)protein,SR protein kinase and other enzymes participate in the composition of alternatively spliced tissue factor(asTF). Recently researchers have found that this protein takes a part in tumor angiogenesis,tumor progression,metastasis and so on,so the detection of its clinical content will be very significant.

Outcomes of imatinib and allogeneic hematopoietic stem cell transplantation in the treatment of chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the curative effect of imatinib and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the treatment of chronic myeloid leukemia (CML).</p><p><b>METHODS</b>292 CML patients received imatinib, and 141 patients underwent allo-HSCT. The clinical data of these patients were retrospectively analyzed to compare event- free survival (EFS) and overall survival (OS) between these two groups of patients in chronic and advanced (including accelerate and blast) phases.</p><p><b>RESULTS</b>(1) EFS, OS, expected 5- year EFS and OS of imatinib group (278 patients in chronic phase) were all statistically higher than of allo-HSCT group (120 patients in chronic phase) (88.5% vs 70.0%, 93.2% vs 80.0%, 84.0% vs 75.0% and 92.0% vs 79.0%, respectively, all P values < 0.01). (2) EFS and OS of imatinib group (14 patients in accelerate and blast phases) were 42.9% and 42.9%, respectively. Meanwhile EFS and OS of allo-HSCT group (21 patients in accelerate and blast phases) were 47.6% and 57.1%, respectively. There were no significant differences in terms of EFS and OS between the two groups (P values>0.05).</p><p><b>CONCLUSION</b>EFS and OS of imatinib group were significantly higher than of allo-HSCT group for CML patients of in chronic phase. Imatinib and allo-HSCT had the similar efficacy for CML patients in accelerate and blast phases.</p>

Efficacy analysis of haploidentical allogeneic hematopoietic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia / 中国实验血液学杂志

This study was aimed to explore the effect and feasibility of related haploidentical allogeneic hematopoietic stem cell transplantation (hi-HSCT) used in the treatment of patients with Ph⁺ ALL. A total of 22 patients with Ph⁺ ALL received related hi-HSCT from March 2008 to August 2013. The clinical data of all cases were retrospectively analyzed.There were 15 cases of CR1, 3 cases of CR2, 1 case of CR3 and 3 cases of relapse. The bone marrow and peripheral blood stem cells of related haplotype donors were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan (Bu), cyclophosphamide and tota1 body irradiation (TBI), etc. GVHD was prevented by combining variety of immunosuppressants including CsA, MTX, MMF and ATG, etc. The results showed that all of 22 patients acquired hematopoietic reconstitution, and the median time of granulocytes exceeding 0.5 × 10⁹/L and platelets exceeding 20 × 10⁹/L which were transplanted by donors were 13 days and 23 days respectively. The mean follow-up period was 13 months. Ten patients had experience of aGVHD, and 8 patients had experience of cGVHD. Two patients died of infection, 3 died of GVHD and 3 died of relapse,and the rest patients were alive in disease-free situation at lase follow-up. The 2-year disease-free surviva1 rate was 57%. It is concluded that related hi-HSCT can prolong disease-free survival of Ph(+)ALL patients and even cure.

Self-renewal mechanism of cancer stem cells / 国际肿瘤学杂志

Cancer stem cells comprise a sub-population with the capacity of self-renewal,self-differentiation and high tumorigenicity.Cancerogenesis,development,relapse and therapeutic resistance are closely related with these cells.The most important characteristics of these cells are the ability to self-renew.So insight into the regulating mechanism of self-renewal in cancer stem cells will be important for the development of novel molecular agents targeted the cancer stem cells.