Advances in key pathogenesis of atypical acute promyelocytic leukemia and mechanisms of all-trans retinoic acid resistance / 白血病·淋巴瘤

Due to the successful application of all-trans retinoic acid (ATRA) and arsenic, the treatment of acute promyelocytic leukemia (APL) with PML::RARA fusion gene has achieved great success. However, some patients are presented with APL phenotype in cellular morphology, immunophenotype, and gene expression profile, while PML::RARA is negative, which is known as atypical APL (aAPL). In aAPL patients, more than 20 fusion genes related to retinoic acid receptors have been reported. It has been discovered that all evaluable patients with RARG fusion genes and approximately half of those with rare RARA fusion genes are resistant to ATRA, however, the molecular mechanisms of this resistance remain poorly studied. Combining with the reports in the 65th American Society of Hematology Annual Meeting, this paper reports great progresses of the key pathogenesis of aAPL and ATRA resistance mechanisms.

Construction and drug resistance evaluation of cell strains which stably express FIP1L1-PDGFRA protein and its mutants / 基础医学与临床

Objective To construct mouse BaF3-FIP1L1-PDGFRA(F/P),BaF3-F/P-T674I and BAF3-F/P-D842V pre-B cell strains which stably express F/P fusion protein and its T674I and D842V mutants in order to e-valuate their activity by checking their responses to tyrosine kinase inhibitors(TKIs).Methods Lentivirus infected technique was used to transfect the target gene into BaF3 cells.RT-qPCR was used to detect mRNA expression,and CCK-8 method was used to detect the inhibitory effect of TKIs on the proliferation of stable cell strains.Results The constructed BaF3-F/P,BaF3-F/P-T674I and BAF3-F/P-D842V cell strains all transcripted FIP1L1 and PDGFRA mRNA.They exhibited malignant phenotypic characteristics of proliferation independent of IL-3 and sen-sitivity to corresponding TKIs.Conclusions The pre-B-cell strains stably expressing F/P and its T674I and D842V mutants are successfully constructed,which provide a good cell model for the development of compounds targeting at those molecules.

Evaluation of the therapeutic value of FISH signaling type and chromosome karyotype analysis in ETV6/RUNX1-positive pediatric B-ALL / 临床与实验病理学杂志

Purpose To explore the diagnostic value of dif-ferent fluorescence in situ hybridization(FISH)signal types and chromosomal karyotyping analysis in ETV6/RUNX1-positive B-cell acute lymphoblastic leukemia(B-ALL).Methods Clini-cal data of 164 newly diagnosed ETV6/RUNX1-positive B-ALL patients were collected for retrospective analysis of chromosomal karyotyping and FISH.Results Among the 164 patients,163 positive cases were detected by FISH,among them the classic 2F1R1G signal type was found in 61 cases,and 102 cases showed non-classic signal types,with 2F1G and 1F1R2G signal types being the most common,indicating ETV6 deletion.Among them,the classic 2F1R1G signal type was found in 61 cases,and 102 cases showed non-classic signal types,with 2F1G and 1F1R2G signal types being the most common,indicating ETV6 deletion.Among the 125 children who could undergo karyoty-ping analysis,106 had a normal karyotype and 19 had an abnor-mal karyotype,with no detection of t(12;21)translocation.Conclusion FISH technology has high sensitivity in detecting ETV6/RUNX1 fusion genes,and it often manifests as non-clas-sic signal types,including ETV6 deletions.Chromosomal karyo-typing analysis helps to identify complex karyotypes and polyploidy but is not conducive to detecting t(12;21)fusion.Therefore,both FISH signal types and karyotyping analysis play indispensable roles in ETV6/RUNX1-positive B-ALL.

Clinical features of 19 patients with SIL-TAL1-positive T-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: To assess the clinical characteristics and prognosis of patients with SIL-TAL1-positive T-cell acute lymphoblastic leukemia (T-ALL) . Methods: The clinical data of 19 SIL-TAL1-positive T-ALL patients admitted to the First Affiliated Hospital of Soochow University between January 2014 and February 2022 were retrospectively computed and contrasted with SIL-TAL1-negative T-ALL patients. Results: The median age of the 19 SIL-TAL1-positive T-ALL patients was 15 (7 to 41 years) , including 16 males (84.2%) . SIL-TAL1-positive T-ALL patients had younger age, higher WBC, and hemoglobin compared with SIL-TAL1-negative T-ALL patients. There was no discrepancy in gender distribution, PLT, chromosome abnormality distribution, immunophenotyping, and complete remission (CR) rate. The 3-year overall survival (OS) was 60.9% and 74.4%, respectively (HR=2.070, P=0.071) . The 3-year relapse-free survival (RFS) was 49.2% and 70.6%, respectively (HR=2.275, P=0.040) . The 3-year RFS rate of SIL-TAL1-positive T-ALL patients was considerably lower than SIL-TAL1-negative T-ALL patients. Conclusion: SIL-TAL1-positive T-ALL patients were connected to younger age, higher WBC, higher HGB, and poor outcome.

Genotype and Phenotype of α-Thalassemia Fusion Gene in Huadu District of Guangzhou, Guangdong Province of China / 中国实验血液学杂志

OBJECTIVE@#To explore the carrier rate, genotype and phenotype of α-thalassemia fusion gene in Huadu district of Guangzhou, Guangdong province of China, and provide data reference for the prevention and control of thalassemia.@*METHODS@#A total of 10 769 samples who were screened for thalassemia in Maternal and Child Health Hospital of Huadu District from July 2019 to November 2020 were analyzed retrospectively. Blood cell analysis and hemoglobin (Hb) electrophoresis were performed. Thalassemia genes were analyzed by gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB).@*RESULTS@#A total of 9 cases with α-thalassemia fusion gene were detected in 10 769 samples (0.08%). There were 7 cases with fusion gene heterozygote, 1 case with compound of α-thalassemia fusion gene and Hb G-Honolulu, 1 case with compound of α-thalassemia fusion gene and Hb QS. The MCV results of 4 samples of blood cell analysis were within the reference range, the Hb A2 value of 1 case was decreased, and there were no other abnormalities found.@*CONCLUSION@#The α-thalassemia fusion gene is common in Huadu district of Guangzhou, and heterozygotes are more common, and current screening methods easily lead to misdiagnosis.

Lung Squamous Cell Carcinoma with EML4-ALK Fusion and TP53 Co-mutation Treated with Ensartinib: A Case Report and Literature Review / 中国肺癌杂志

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

Clinical Analysis of SET-NUP214 Fusion Gene Positive Patients with Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene.@*METHODS@#The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively.@*RESULTS@#Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive.@*CONCLUSION@#The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.

Primary renal synovial sarcoma: a case report / 中华泌尿外科杂志

Primary prostate synovial sarcoma (PPSS) is rare in clinic. One patient was admitted to our hospital in May 2021. The patient was admitted to the hospital because of the physical examination. Preoperative pelvic enhanced MR, PETCT and preoperative puncture pathology suggested that pelvic soft tissue sarcoma was likely. Robot-assisted radical resection of pelvic tumor was performed, and the unilateral PPSS was diagnosed by postoperative pathology, immunohistochemistry and gene detection. Patients were treated with ifosfamide + adriamycin adjuvant chemotherapy one month after operation, and Proton therapy radiotherapy five months after operation. Follow-up for more than 2 years showed that the patients were generally in good condition, and no recurrence or metastasis was found in imaging.

Analysis of clinical characteristics and prognosis of newly-treated acute lymphoblastic leukemia patients with MLL-AF4 fusion gene-positive / 白血病·淋巴瘤

Objective:To investigate the development of MLL-AF4 fusion gene-positive in newly-treated acute lymphoblastic leukemia (ALL) and to analyze the clinical characteristics and prognosis of patients with MLL-AF4 fusion gene-positive ALL.Methods:The clinical data of 455 patients with primary newly-treated ALL from February 2010 to February 2021 in Zhumadian Central Hospital were retrospectively analyzed. Fluorescence in situ hybridization was used to detect the presence of MLL gene rearrangement, and multiplexed nested reverse transcription polymerase chain reaction was used to detect the development of MLL-AF4 fusion gene-positive, and to compare the clinical characteristics and prognosis of patients with positive and negative MLL-AF4 fusion gene.Results:Among 455 patients with primary newly-treated ALL, 30 cases (6.6%) were positive for MLL gene rearrangement, including 21 positive for MLL-AF4 fusion gene (MLL-AF4 positive group), 6 cases positive for MLL-ENL fusion gene, 2 cases positive for MLL-AF9 fusion gene, and 1 case positive for MLL-AF10 fusion gene. A total of 60 ALL patients without any detection of fusion gene during the same period were randomly selected as the MLL-AF4-negative group. The proportion of those with hepatomegaly or splenomegaly, central nervous system (CNS) invasion, and the median peripheral blood leukocyte count and median peripheral blood na?ve cells absolute value in the MLL-AF4-positive group were higher than those in the MLL-AF4-negative group (all P < 0.05). The complete remission rates on day 15 of chemotherapy were 81.0% (17/21) and 90.0% (54/60), respectively in the MLL-AF4-positive group and MLL-AF4-negative group ( χ2 = 0.49, P = 0.484), and the cumulative relapse rates of 3 months were 38.1% (8/21) and 13.3% (8/60), respectively in the MLL-AF4-positive group and MLL-AF4-negative group ( χ2 = 4.56, P = 0.033). The overall survival in the MLL-AF4-positive group was worse than that in the MLL-AF4-negative group ( χ2 = 5.93, P = 0.015). Conclusions:Patients with MLL-AF4 fusion gene-positive ALL have a higher tumor load, a higher recurrence rate, a lower overall survival rate, and a poorer prognosis compared with negative patients at the initial diagnosis.

Clinical characteristics and prognosis analysis of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.

Acute leukemia with NUP98-DDX10 fusion gene-positive: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of acute leukemia (AL) with NUP98-DDX10 fusion gene-positive.Methods:The clinical data of 2 AL patients with NUP98-DDX10 fusion gene-positive who admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences in April 2020 and February 2021, respectively were retrospectively analyzed. Transcriptome gene sequencing was used to detect fusion gene, and the fusion gene fragment was amplified by using reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing was used to clarify sequences. The clinical and experimental indicators characteristics were analyzed and the relevant literatures were reviewed.Results:According to the clinical diagnosis, 1 patient was diagnosed as acute myeloid leukemia M 5 (AML-M 5) and 1 patient was diagnosed as acute leukemia of ambiguous lineage, not otherwise specified (ALAL-NOS). The AML-M 5 patient presented with severe coagulation abnormalities, and fulfilled the diagnostic criteria for diffuse intravascular coagulation (DIC) at the initial visit. Transcriptome sequencing of 2 patients showed NUP98-DDX10 fusion gene- positive. RT-PCR confirmed that sequencing results identified 2 different splice fusion modes: one was NUP98 exon 14 fused with DDX10 exon 7(usually called "type Ⅱ"), the other was NUP98 exon 14 fused with DDX10 exon 13, which was never reported and named as "type Ⅳ". From 1997 to 2018, a total of 16 cases with NUP98-DDX10 related hematologic neoplasms were reported in the literature. A summary analysis of 16 cases added with 2 patients in our center included 13 males and 5 females with median age 31.5 years (0.08-61 years). The median overall survival was 12 months (1-46 months). Conclusions:A novel fusion gene NUP98-DDX10 transcriptome is identified in ALAL-NOS patient. Hematological malignancies with NUP98-DDX10 are very rare. They respond poorly to conventional treatment and require allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve the prognosis.

Progress of BCR-ABL fusion gene and JAK2 V617F mutation double-positive myeloproliferative neoplasms / 白血病·淋巴瘤

Myeloproliferative neoplasms (MPN) are a group of clonal disorders of hematopoietic stem cells, and JAK2 V617F gene mutation is the main basis for the diagnosis of MPN. Previous studies have shown that BCR-ABL fusion gene and JAK2 V617F gene mutation are mutually exclusive in MPN patients, but in recent years, patients with a double mutation of both genes are often reported. The article synthesizes the relevant domestic and foreign literature in recent years, and reviews the BCR-ABL fusion gene and JAK2 V617F mutation double-positive MPN.

A case of acral fibrochondromyxoid tumor / 中华皮肤科杂志

A 44-year-old male patient presented with a subcutaneous nodule in the left little finger for 3 years. Skin examination showed a subcutaneous nodule with rubber-like hardness but no tenderness on palpation, measuring 0.4 cm × 0.4 cm in size at the dorsal distal aspect of the left little finger, and the movement of the distal interphalangeal joint was unrestricted. Postoperative histopathological examination revealed that the tumor contained abundant stroma consisting of variable fiberous, chondroid and myxoid materials; tumor cells were oval to short spindle-shaped with inconspicuous nucleoli but no mitosis; cells were arranged haphazardly or in small clusters. Immunohistochemical study showed positive staining for vimentin, CD34 and transcription factors ERG and SOX9, but negative staining for S100, P63, broad-spectrum cytokeratin AE1/AE3, epithelial membrane antigen, smooth muscle actin and desmin in tumor cells, and the Ki67 labeling index was below 1%. Finally, the patient was diagnosed with acral fibrochondromyxoid tumor.

Mechanism of BCL2L2-PABPN1 expression induced by sodium arsenite and its metabolites in 16HBE cells / 中国职业医学

@#Objective - - （BCL2L2）- （ ） To investigate the differential expression of the fusion gene BCL 2 like protein 2 poly A （PABPN1） （ ） binding protein nuclear 1 induced by sodium arsenite SA and its methylated metabolites in 16HBE cells and the Methods ） ， related mechanism. i The 16HBE cells exposed to SA at concentrations of 1.5 3.0 and 4.5 µmol/L were set as -， - - low medium and high dose arsenic exposure groups. The 16HBE cells exposed to 4.5 µmol/L monomethylarsonic acid （ ）， （ ） ， MMA dimethylarsonic acid DMA and SA were set as MMA group DMA group and SA group. The 16HBE cells without ， BCL2L2-PABPN1 toxic stimulation were set as control group. After the cells were cultured for 48 hours the expression of was - （ - ） ） （ ） detected by quantitative real time polymerase chain reaction qRT PCR . ii Two small interfering RNA siRNA silencing 基金项目：国家自然科学基金（ ）； 年云南省科技厅昆明医科大学应用基础研究联合专项面上项目 82160607 2021 （ ） 202101AY070001-054 作者简介：施雅（ —），女，在读大学本科生，主要从事劳动卫生与环境卫生学研究；尹锦瑶（ —），女，在读劳动卫生与环境卫 2001 1995 生学硕士研究生，主要从事劳动卫生与环境卫生学研究；施雅和尹锦瑶为共同第一作者 通讯作者：何越峰教授，博士研究生导师，- ： E mail heyuefeng@kmmu.edu.cn中国职业医学 年 月第 卷第 期 ， ， ， · · 2022 10 49 5 Chin Occup Med October 2022 Vol.49 No.5 523 BCL2L2-PABPN1， - fragments were designed and transfected into 16HBE cells to knockdown which were set as siRNA 1 group - - BCL2L2-PABPN1 and siRNA 2 group. Non transfected control group without knockdown of transfection was set up. After ， BCL2L2-PABPN1 - culturing for 48 hours the expression level of in the three groups of cells was detected by qRT PCR. The cell - survival rate and early apoptosis rate were detected by MTS method and JC 1 mitochondrial membrane potential detection ， （ ） ， method respectively. The apoptosis was detected by Hoechest33342/propidium iodide PI double staining and the expression - Results ） level of P53 signaling pathway related proteins was detected by Western blotting. i The relative expression of BCL2L2-PABPN1 （P ） BCL2L2- in 16HBE cells increased with the increasing SA doses <0.01 . The relative expression of PABPN1 - ， - - in high dose arsenic exposure was higher than that in control group low dose and medium dose arsenic exposure （ P ） BCL2L2-PABPN1 ， groups all <0.05 . The relative expression of in SA group was higher than those in control group MMA （ P ） BCL2L2-PABPN1 group and DMA group all <0.05 . The relative expression of showed no significant difference between ， （ P ） ） BCL2L2-PABPN1 control group MMA group and DMA group all >0.05 . ii The relative expression levels of and cell - - - （ P ） survival rate in siRNA 1 group and siRNA 2 group were lower than those in non transfected control group all <0.05 . ， （P ） However there was no significant difference in the early apoptosis rate among the three groups >0.05 . The results of - Hoechest33342/PI double staining showed that the number of nuclear shrinkage and early apoptotic cells in siRNA 1 group and - - ， - siRNA 2 group was higher than that in non transfected control group. The relative protein expression levels of P53 phospho ， - - ， - - （ P ） p53 BCL 2 associated death promoter P21 and cytochrome C in siRNA 1 group and siRNA 2 group were higher all <0.05 , - - P and the relative protein expression levels of P53 up regulated modulator of apoptosis were lower (all <0.05), when compared - Conclusion with the non transfected control group. SA may block the apoptosis of 16HBE cells by inducing the expression of BCL2L2-PABPN1 fusion gene . The mechanism may be related to the activation of P53 signaling pathway. The SA methylated BCL2L2-PABPN1 BCL2L2-PABPN1 - metabolites MMD and DMA had no effect on the expression of . may affect anti apoptosis BCL2L2 PABPN1 through affecting the synergistic effect of and genes.

The Factors Affecting Relapse in Pediatric B-cell Acute Lymphoblastic Leukemia Patients without Prognostic Fusion Genes Following Up for 10 years / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients.@*METHODS@#B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients.@*RESULTS@#There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients.@*CONCLUSION@#Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.

Research progress on pathogenic fusion gene in lung cancer / 中国临床药理学与治疗学

Lung cancer is one of the most harmful global diseases with high morbidity and mortality rate. As a unique kind of driver gene, the pathogenic fusion gene is a common mechanism of lung cancer. Most fusion genes are produced by chromosome rearrangement and encoding receptor tyrosine kinases, which could be potential lung cancer therapeutic targets. Since ALK was first identified in 2007, methods like FISH, IHC, RT-PCR and NGS have been intensively applied, leading to identification of multiple other lung cancer fusion genes including ROS1, RET, FGFR, NTRK1, NRG1, DNAH5 and LTK. These works broaden the spectrum of lung cancer related gene mutations, and support the customized treatment for clinical patients. For some fusion genes, corresponding kinase inhibitors have been developed with good efficacy, however, the treatment is still being challenged by several problems like drug resistance. Based on recent studies, the research development of lung cancer fusion genes will be discussed.

Clinical features and prognosis analysis of acute myeloid leukemia patients with DEK-CAN-positive / 白血病·淋巴瘤

Objective:To investigate the clinical features and prognosis of patients with acute myeloid leukemia (AML) with DEK-CAN-positive.Methods:The clinical data of 6 AML patients with DEK-CAN-positive admitted to the First Affiliated Hospital of Zhengzhou University from August 2014 to January 2018 were retrospectively analyzed. Their clinical features, treatment and outcomes were summarized.Results:All 6 patients were female with a median age of 29 years (4-64 years). Among 6 cases, 5 cases were primary granulocytic leukemia partially differentiated (M 2) and 1 case was acute monocyte leukemia (M 5). There were 5 patients with elevated count of white blood cells in peripheral blood, and 1 patient had bone marrow dysplasia, and 2 patients had basophilia. Immunophenotypic analysis showed that all 6 patients were positive for CD34, CD13, CD38 and CD33. Fusion gene detection showed that DEK-CAN was positive and NPM1 mutations were negative in 6 patients; FLT3-ITD mutation was detected in 3 patients and WT1 mutation was detected in 2 patients. Chromosomal karyotyping showed that 2 cases had no split phase and 4 cases carried t(6;9). Follow-up details were available for 6 patients, only 1 patient achieved complete remission after the first course of induction chemotherapy, and the remaining 5 patients had no complete remission after the first course of chemotherapy, and died of complications in a short time. Conclusion:AML patients with DEK-CAN-positive have a very poor prognosis, low primary induced remission rate and high mortality.

Research Progress of Fusion Genes RET in Non-small Cell Lung Cancer / 中国肺癌杂志

In the past 20 years, with the development of molecular biology, the treatment of non-small cell lung cancer (NSCLC) has been developing. Targeted therapy has improved the survival period of patients with positive mutation of tumor driver gene. More and more targets have been found gradually. Drugs targeting different driving genes have brought the treatment of NSCLC into a promising target era. Among the many driving genes of NSCLC, the fusion of transfection proto oncogene (RET) is the addition of the epidermal growth factor receptor (EGFR), analytic lymphama kinase (ALK) and c-ros oncogene 1-receptor tyrosine kinase (ROS1) are emerging targets. Targeted drugs for RET gene fusion have been constantly updated. Recently, new high selective RET inhibitors blu-667 and loxo-292 have made important breakthroughs. This paper will review the review of the fusion mutation of RET gene in NSCLC, the detection methods, clinicopathological characteristics, targeted treatment and the research progress after drug resistance.
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A Case of Non-small Cell Lung Cancer Treated with Three ALK Inhibitors and Chemotherapy / 中国肺癌杂志

The echinoderm microtubule associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) were fractured and fused to become EML4-ALK. Most of these EML4-ALK-positive non-small cell lung cancer patients respond well to the ALK inhibitor. Many patients can benefit from drug target therapy for a long time, and some patients can achieve long-term survival of more than 7 years under the optimized treatment mode. This patient has lung adenocarcinoma positive for EML4-ALK fusion gene, but the treatment outcome is obviously different from that of other patients with lung cancer positive for EML4-ALK fusion gene. After the first to third generations of ALK inhibitor targeted therapy and chemotherapy, the disease progresses rapidly, the drug resistance time is short, the survival time is short, and the benefit is limited. The patient received targeted therapy of Crizotinib, Ceritinib and Lorlatinib successively from July 15, 2019, followed by two chemotherapy courses of Bevacizumab combined with Pemetrexed and Carboplatin. The patient died on September 10, 2020, with a survival of 15 months. At the same time, the treatment showed common adverse reactions of ALK inhibitors. This paper analyzed the therapeutic effect and treatment dilemma of this patient, and provided an exploration direction for the treatment of patients with EML4-ALK fusion gene positive lung cancer.
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