[The Application Study of Voriconazole and Its Metabolites Concentration Monitoring in Allogeneic Hematopoietic Stem Cell Transplantation Patients].

OBJECTIVE: To explore the application value of simultaneous monitoring of voriconazole (VRCZ) and voriconazole N-oxide (VNO) in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients before engraftment (i.e., days +1 to +30 after transplantation). METHODS: The influencing factors of VRCZ, VNO concentration and MR (CVNO/CVRCZ) and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed. The receiver operating characteristic curve (ROC) was used to analyze the differences (the corresponding to the maximum of the Youden index on the curve was set as the cut-off value) to confirm the critical value. RESULTS: The factors affecting VRCZ concentration (CVRCZ), VNO concentration (CVNO) and MR were patient weight, VRCZ daily dose, and transplantation type (all P < 0.05). CVRCZ and CVNO in the effective group were higher than those in the ineffective group (P < 0.001), the opposite of MR (P < 0.001); the liver and renal injury group had lower MR than the normal group (P < 0.05). ROC showed that CVRCZ, C VNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment, and their cutoff of concentrations were 0.95 µg/ml, 1.35 µg/ml and 1.645, respectively (AUC: 0.9677, 0.7634, 0.9564). CVRCZ and MR can assist in indicating liver ï¼»cutoff values: 0.65 µg/ml, 1.96 (AUC: 0.5971, 0.6663)ï¼½ and renal injury ï¼»cutoff values: 0.95 µg/ml, 1.705 (AUC: 0.6039, 0.6164)ï¼½. CONCLUSION: The great value of simultaneous monitoring of VRCZ, VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment. The prediction accuracy of CVRCZ was higher than that of MR, followed by that of CVNO. Increased CVRCZ and decreased MR increase the risk of liver and kidney injury.

Characteristics and literature review of ETV6::ABL1 fusion gene-positive acute myeloid leukemia.

OBJECTIVE: To describe the features of ETV6::ABL1 AML as well as the clinical treatment and outcomes. METHODS: Clinical data were collected from three patients diagnosed with ETV6::ABL1 AML at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital. Their clinical and laboratory features were analyzed, and the treatment process and outcomes were described. Ten reported cases of ETV6::ABL1 AML from the literature were also included for analysis. RESULTS: The median age of the patients was 34 years, and 2 patients were male. No patient had a history of blood disorders before diagnosis. After relapse, they were referred to our hospital, where the ETV6::ABL1 gene was detected. Unfortunately, Patient 1 died rapidly after leukemia relapse due to severe infection. Patients 2 and 3 received salvage therapy with a dasatinib-containing regimen, followed by allo-HSCT, and are currently alive and disease-free. CONCLUSION: ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative.

A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

[Development and Application of Automatic Analysis and Surveillance Platform for Chrimerism in Donors and Recipients after Allo-HSCT].

OBJECTIVE: To develop an automated chimeric analysis and reporting platform based on short tandem repeat (STR) and capillary electrophoresis methods for allogeneic hematopoietic stem cell transplantation (allo-HSCT) so as to improve work efficiency. METHODS: Apache, MySQL, PHP and HTML5 were used to build the database and interface. The STR locus geno typing and chimeric analysis logic and flow were set up on the basis of STR rules and capillary electrophoresis. STR genotyping and 194 times of chimeric testing data of 100 patients after allo-HSCT were used to test the platform for automatic STR locus genotyping, chimeric calculation and report generation. RESULTS: The established platform could realize the functions of STR locus customization, STR genotype determination, automatic chimeric analysis, and detection information database management, which can automatically generate an integrated report including multiple sequential chimeric results and trend graphs for the same patient and can be accessed and used simultaneously by different users through different browser interfaces. The results of automated analysis by the platform are completely consistent with that of manual analysis by experienced technicians, and the possibility of manual analysis error is reduced through automation. The time required for automatic analysis using this platform is approximately 1/6-1/5 of manual analysis. CONCLUSION: The automatic analysis platform built in this study is operation stable and reliable in analysis results, which can improve work efficiency and report connotation, thus worthing popularized and applicable.

[Analysis of Correlation between Gene Mutation and Age in Patients with MDS and MDS/AML].

OBJECTIVE: To study the correlation between tumor-associated somatic gene mutation and age in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from myelodysplastic syndrome (MDS/AML). METHODS: A total of 111 patients primarily diagnosed as MDS or MDS/AML were selected. Bone marrow samples from patients were collected or bone marrow smears prepared at the initial diagnosis were used for detecting the somatic gene mutations of 58 genes related with hematologic tumors by high-throughput gene sequencing. And the correlation of gene mutations with the age of patients was analyzed. RESULTS: The positive rate of total gene mutation was 87.39% (97/111) in 111 patients, and 231 mutations in 28 different genes were detected in the patients with positive gene mutation. The patients of mutation-positive group were significantly older than that of the mutation-negative group (P＜0.001). Among the mutation-positive patients, the mutation rate in the senile group (≥60 years) was 100% (14/14), followed by 89.04% (74/85) in the adult group (15-59 years) and 75% (9/12) in the children group (≤14 years). The average number of mutations in the children group, the adult group and the senile group were respectively 1.44, 2.47 and 2.5; the number of mutations in the adult group was greater than that in the children group (P＜0.05).The most common mutations in the children group occurred in signal transduction gene (46.15%, 6/13); The most common mutations in both the adult group (22.40%, 41/183) and the senile group (34.29%, 12/35) occurred in epigenetic regulatory gene; the mutation rate of transcription factor gene in the senile group was higher than that in the children group (50.00% vs 8.33%) (P＜0.05); the mutation rates of the splicing factor gene in the adult group and the senile group were higher than that in the children group (44.71% vs 8.33%) (P＜0.05), (47.06% vs 8.33%) (P＜0.05). CONCLUSION: The tumor-associated somatic gene mutations in patients with MDS and MDS/AML are significantly different between the different age groups, especially the children group and the adults group as well as the senile group, suggesting that the occurrence of MDS in children may involve genetic factors that are significantly different from those of adults and the senile.

[Analysis of Human Herpes Viruses-Activated Infection Spectra in Patients with Various Immunodeficiencies].

OBJECTIVE: To study the epidemiologic characteristics of human herpes virus (HHV) activated infection in the diseases of blood system and patients received allo-HSCT by statistically analyzing the screening results of 8 human herpes viruses (HHVs) of 4164 patients in Hebei Yanda LU Dao-Pei Hospital from 2012 to 2017. METHODS: PCR was used to screen 8 HHVs. RESULTS: Two thousand and fifty-two patients (49.28%) were HHV-positive among 4164 patients screened. Among these patients screened, the infection spectra of 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation of totally 2994 patients were summarized as follows: the positive rate of EBV (29.49%) was the highest, that of HCMV (23.15%), HHV-6 was 18.77% and HHV-7 was 17.64%, while the remaining 4 HHVs all≤2.1%. The rate of co-infection of various HHVs was significantly higher than that of single infection of HHV among all these disease groups except familial hemophagocytic lymphohistiocytosis, for which single EBV infection was the most common. The differences of positive rates among these 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation were statistically significant by Chi-square test of R*C tables (χ2=54.99, P＜0.05). For each HHV, the differences of positive rates among the above-mentioned disease groups were also statistically significant except HHV-8 (P＜0.05). CONCLUSION: The patients with various blood diseases have different activated infection spectra of HHVs. EBV, HCMV, HHV-6 and HHV-7 are most common in HHVs infection. Different HHVs infections correlate with different hematologion diseases.

Conversion to resectability using transcatheter arterial chemoembolization alternating with mFOLFOX6 in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is one of the most common malignancies in the world, and about 25% of colorectal cancer patients present with colorectal cancer liver metastases (CRCLM) even at new diagnosis. The study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) alternating with mFOLFOX6 in Chinese patients with unresectable CRCLM. MATERIALS AND METHODS: In this study, by combining the systemic and regional treatment, the resectability rate, overall survival, and progression-free survival were measured with addition of TACE. Included patients had Eastern Cooperative Oncology Group performance status 0-2. Sixty-two patients received mFOLFOX6 plus one TACE after 2 weeks of chemotherapy; after 2 weeks, the next periodical treatment repeated. Patients received operation when the liver metastases were converted to resectability or severe tumor-associated complications occurred. RESULTS: We found that 28 patients (45.2%) patients received operation after the treatment of TACE combined with systemic chemotherapy. The median time from initial treatment to the operation was 6 months. The median follow-up period was 41 months in all the patients. The 3-year survival rate of resected patients and unresected patients was 54% and 17%, respectively. Post-TACE syndrome was the major adverse reaction (81%). Other adverse reactions were neutropenia, nausea, and neurotoxicity. No patient died of the adverse reactions. The resection rate was related to hepatic segments and vasculature involvement. CONCLUSION: Taken together, TACE alternating with mFOLFOX6 has been proved to be safe and effective for CRCLM treatment to improve resection rate and prolong the survival time.

Cytotoxic Triterpenoids from Roots of Actinidia chinensis.

Phytochmical investigation of roots of Actinidia chinensisPlanch. led to the isolation triterpenoids 1 - 16, including a new compound 2α,3α,23,24-tetrahydroxyursa-12,20(30)-dien-28-oic acid (1). Their structures were identified on the basis of spectroscopic analysis, including 1D- and 2D-NMR, HR-ESI mass spectrometry, and by comparison with the literatures. The cytotoxicities of triterpenoids 1 - 16 against a panel of cultured human cancer cell lines (HepG2, A549, MCF-7, SK-OV-3, and HeLa) were evaluated. The new compound 1 exhibited moderate antitumor activities with IC50 values of 19.62 ± 0.81, 18.86 ± 1.56, 45.94 ± 3.62, 62.41 ± 2.29, and 28.74 ± 1.07 µm, respectively. The experiment data might be available to explain the use of roots of A. chinensis to treat various cancers in traditional Chinese medicine.

[Chemical constituents from roots of Actinidia rufa and their cytotoxicity].

To investigate the chemical compounds from the roots of Actinidia rufa, nine compounds were isolated by various column chromatography on silica gel and Sephadex LH-20, and high performance liquid chromatography (HPLC). Their structures were elucidated as 2α, 3ß, 19α, 23, 24-pentahydroxyurs-12-en-28-oic acid-28-O-ß-D-glucopyranoside (1), 2α, 3α, 19α, 24-tetrahydroxyurs-12-en-28-oic acid-28-O-ß-D-glucopyranoside (2), 2α, 3α, 24-trihydroxyurs-12-en-28-oic acid (3), 2α, 3α, 24-trihydroxyolean-12-en-28-oic acid (4), 2α, 3α, 23, 24-tetrahydroxyurs -12-en-28-oic acid (5), 2α, 3ß, 23, 24-tetrah-ydroxyurs-12-en-28-oic acid (6), 2α, 3ß, 23-trihydroxy-12-en-28-oic acid (7), 2α, 3ß, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (8), and 2α, 3α, 23-trihydroxyurs-12, 20(30)-dien-28-oic acid (9). Compounds 1 and 2 were isolated from the Actinidia genus for the first time. Compounds 2, 3, and 4 showed cytotoxic activity against human SKVO3 and TPC-1 cancer cell lines with IC50 values ranging from 10.99 to 16.41 µmol•L⁻¹, compounds 3 and 4 have cytotoxic activity against human HeLa cancer cell line with IC50 values of 15.53 and 13.07 µmol•L⁻¹, respectively.

[Advances in Research and Application of Liquid Biopsy in Lymphoma-Review].

Liquid biopsy as a new rising non-invasive testing method play an important role in assisting diagnosis, evaluating efficacy and prognosis, monitoring early recurrence and drug resistance. It has been widely applied in some types of solid tumors. Lymphoma is a group of heterogeneous hematological malignancies, among which most subtypes without specific tumor markers, and the evaluation of the efficacy and prognosis mainly depend on biopsy and imaging. Compared with other solid tumors, lymphoma cells were characterized by a trend to enter in peripheral circulation, and the diversity of immunoglobulin molecules can be monitored as marker, which can be applicable to liquid biopsy. With the advances in detection technology, research and application of liquid biopsy in lymphoma have attracted more attentions. In this review, the concept of liquid biopsy, base for liquid biopsy and its current situation of performance, progress of research and performace of liquid biopsy in lymphoma and so on are summarized.

Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion gene.

We report the clinical features and outcome of 22 TLS-ERG+ leukemia patients (20 AML and 2 B-ALL). TLS-ERG was tightly associated with extramedullary disease (EMD), complex chromosome abnormalities, and high risk gene mutations including IKZF1, WT1, TET2, NOTCH2, and PHF6. The 6-month leukemia free survival (LFS) with and without EMD was 75% and 83.3% (p = .017). 11/20 AML patients received allogeneic hematopoietic stem cell transplantation (HCT). The 1-year overall survival (OS) in non-HCT and HCT group was 62.5% and 90% (p = .026), but the 6-month LFS in non-HCT and HCT group was 55.6% and 100% (p = .192). The 6-month LFS of patients with complete remission (CR) before HCT versus those with no response (NR) was 67.5% and 0, respectively (p = .034). In conclusion, the leukemia burden before HCT and EMD had negative impact on the outcome of TLS-ERG patients; HCT could prolong OS, but could not overcome the poor prognostic impact of TLS-ERG.

[Research on ground scenery spectral radiation source with tunable spectra].

A spectrum-tunable ground scenery spectrum radiation source, using LEDs and bromine tungsten lamp as luminescence media, was introduced. System structure and control of the spectrum radiation source was expounded in detail. In order to simulate various ground scenery spectrum distribution with different shapes, a ground scenery spectral database was established in the control system. An improved genetic algorithm was proposed, and a large number of ground scenery spectra were produced by the simulator. Spectral similarity and the average spectral matching error of several typical ground scenery spectra were further analyzed. Spectral similarity of red bands, green bands, blue bands and near-infrared spectral band also was discussed. When the radiance of the target was 50 W x (m2 x sr)(-1), the average spectral matching error was less than 10% and spectral similarity was greater than 0.9, up to 0.983. Spectral similarity of red band, green band, blue band and near-infrared band (especially green band and near-infrared band) was less than that of full-band. Compared with blue band and red band, spectral similarity of green band and near-infrared band low-amplitude maximum can rearch 50%. Ground scenery spectrum radiation source can be used as radiometric calibration source for optical remote sensor, and calibration error, which is caused by objectives and calibration sources spectral mismatch, can be effectively reduced.

Mixed lineage leukemia-septin 5 fusion transcript in de novo adult acute myeloid leukemia with t(11;22)(q23;q11.2): A case report.

The current report presents a case of de novo acute myeloid leukemia (AML) in a 32-year-old male. Cytogenetic analysis showed that the karyotype of the bone marrow cells was as follows: 46,XY,t(11;22)(q23;q11.2)[13]/46,X,-Y,+10,t(11;22)(q23;q11.2)[7]/47,XY,+10,t(11;22)(q23;q11.2)[1]/46,XY[1]. Fluorescence in situ hybridization analysis using a mixed lineage leukemia (MLL)-specific probe showed a split in the MLL gene. Reverse transcription polymerase chain reaction (PCR) analysis demonstrated an MLL-septin 5 (SEPT5) fusion transcript in the patient. Nucleotide sequencing analysis of the PCR product confirmed the fusion between the MLL exon 9 and SEPT5 exon 3, and the product was 521 bp in length. The present study reviewed the clinical and molecular features of the AML with an MLL-SEPT5 fusion gene.

Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer. METHODS: For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate. RESULTS: There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups. CONCLUSIONS: These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.

[Acute myeloid leukemia with t(11;22) (q23;q11.2): two cases report and literature review].

OBJECTIVE: To report two de novo acute myeloid leukemia (AML) patients with t(11;22)(q23;q11.2) and summarize the clinical and biological characteristics. METHODS: Bone marrow cells morphology, immunophenotype, chromosome karyotype, fluorescence in situ hybridization (FISH), PCR and gene sequencing were performed. Clinical manifestation and routine laboratory tests were analyzed. RESULTS: The patients were diagnosed as AML-M2 and AML-M5 by morphology and immunophenotype results. Both patients carried t(11;22)(q23; q11.2) and one of them carried an additional chromosome abnormality. MLL-SEPTIN5 fusion transcript was identified in two patients by RT-PCR and sequencing. The two patients got hematologic complete remission after induction chemotherapy with daunorubicin, homoharringtonine, and cytarabine (DHA) or daunorubicin and cytarabine (DA). One of them relapsed and died during consolidation therapy with intermediate-dose cytarabine. CONCLUSION: Leukemia with t(11;22)(q23;q11.2) chromosome translocation met the clinical and laboratory manifestations of AML. The MLL-SEPTIN5 fusion transcript was the distinctively biological etiology. Patients with t(11;22)(q23;q11.2) were vulnerable to relapse after conventional chemotherapy and had poor prognosis. Allogeneic hematopoietic stem cell transplantation should be recommended as early as possible.

[Comparison study of three methods of digestive tract reconstruction after radical gastrectomy in gastric cancer patients].

OBJECTIVE: To investigate the ideal digestive tract reconstruction methods among three different surgical methods after radical gastrectomy of gastric cancer patients. METHODS: A total of 123 patients who received elective radical gastrectomy for gastric cancer from February 2010 to August 2011 were prospectively enrolled and randomly divided into radical proximal gastrectomy and jejunal interposition group, radical proximal gastrectomy and esophageal with the posterior of residual-stomach group, and radical total gastrectomy and Roux-en-Y esophagojejunostomy group. Patients were followed up for 12 months. Symptoms of reflux esophagitis were observed, gastric emptying tests were done, liver and kidney function was also monitored. The quality of life was documented before operation, and one and twelve months after operation. RESULTS: No significant differences were found among these three groups in the pH value of lower part of esophagus, the blood regular test results and the functional parameters of kidney and liver before and after operation(all P>0.05). Symptoms of reflux esophagitis was reported in 1(2.4%) patients in the jejunal interposition group, 10(24.4%) in esophageal with the posterial of residual-stomach group, and 7(17.1%) in the Roux-en-Y esophagojejunostomy group(P=0.017). There was 1(2.4%), 10(17.1%), and 8(19.5%) patients presented reflux of barium meal in these three groups, respectively (P=0.046). There were no statistically significant difference in PH at the distal esophagus(6.9±0.2 vs. 6.8±0.1 vs. 6.9±0.1, P=0.196). The quality of life was significantly improved one year after surgery in terms of general status, physical function, emotional function, fatigue, nausea/vomiting, pain, constipation, and diarrhea (all P<0.05), with the jejunal interposition superior than the other two methods. CONCLUSION: Three methods of digestive tract reconstruction in radical gastrectomy of gastric cancer patients can improve the health status and the quality of life in gastric cancer patients. Radical proximal gastrectomy and jejunal interposition is the preferred method.

[Clinical analysis of 12 cases of acute myeloid leukemia with Ph chromosome and BCR-ABL positive].

This study was purposed to analyze the characteristics of morphology, immunology, cytogenetic and molecular biology of leukemia cells in 12 AML patients with Ph(+) and their correlation with survival of patients. 12 patients with Ph(+) AML were diagnosed according to diagnostic criteria of WHO and existence of t(9;22) (q34;q11) or t(9;22) abnormality, meanwhile no evidence of CML chronic phase was observed. The results showed that 8 out of 12 cases were confirmedly diagnosed to be AML by morphologic and immunophenotypic examination, 4 cases were diagnosed as myeloid and B lymphocytic mixed acute leukemia. The Ph chromosome was detected in 10 cases by chromosome analysis at the first time of diagnosis, and some of the cases had coexistence of complex chromosome and/or normal karyotype. BCR-ABL transcript was detected in all 12 cases, including 7 cases with b3a2, 1 case with b2a2, 1 case with b2a2 variants, 2 cases with e1a2 and 1 case with e18a2. The 12 cases all got complete remission after chemotherapy and/or gleevec treatment, out of them 3 cases received chemotherapy and gleevec treatment, but 2 cases died; 9 cases received allogeneic hematopoietic stem-cell transplantation (allo-HSCT), 1 case died from relapse, among them 1 case died from transplant complications. The median survival was 24 (8 - 80) months, the overall survival of 3 years was (51.4 ± 17.7)%. It is concluded that the Ph(+) AML is a acute myelogenous leukemia with poor prognosis, but long-term survival may be achieved with HSCT as quick as after complete remission from gleevec and chemotherapy treatment. Meanwhile, the detection of BCR-ABL gene and it variants may be give more opportunity for diagnose and treatment, which can be used as routine screening for newly diagnosed leukemia.

[Relationship between V617F mutation and 46/1 haplotype in JAK2 gene in patients with chronic myeloproliferative diseases and frequencies of 46/1 haplotype in different Chinese nationalities].

Somatic gene V617F mutation in JAK2 is a critical molecular and biological indicator to diagnosis of chronic myeloproliferative disease (MPD). This study was aimed to investigate the genetic background of V617F mutation in 46/1 gene haplotype in Chinese MPD patients, and the frequencies of 46/1 gene haplotype and V617F mutation in three nationalities of Chinese populations. Peripheral blood or bone marrow samples of 150 V617F mutation positive MPD patients, 123 V617F mutation negative MPD patients, 124 healthy Han individuals, 395 healthy Tibetan individuals and 315 healthy Yugu individuals were collected. The allele-specific multiplex PCR method was established, the presence or absence of V617F mutation, the presence or absence of 46/1 haplotype, and the relationship between V617F and 46/1 haplotype were easily identified by agarose gel image. The results showed that the V617F mutation located in the 46/1 haplotype of 88 cases (58.67) among 150 V617F-positive MPD cases. In 814 Chinese healthy individuals including Han, Tibetan, Yugu nationalities, the frequency of the 46/1 gene haplotype was 38.37 without difference in the frequency among different nationalities, and no V617F mutation was found in Chinese healthy populations, The frequency of the 46/1 gene haplotype was 43.09 in V617F mutation negative MPD patients and was 69.33 in V617F mutation positive MPD patients, the latter was obviously higher than former and than that in healthy Han individuals. In conclusion, a multiplex PCR method has been developed that is simple and useful to identify V617F mutation in JAK2 gene and its relationship to the 46/1 haplotype. In more than half of Chinese V617F-positive MPD patients, the V617F mutation locates in 46/1 haplotype in JAK2. The frequencies of 46/1 haplotype are statistically insignificant among Han, Tibetan and Yugu nationality populations.