Ultrasonographic Findings of Xp11.2/TFE3 Translocation Renal Cell Carcinoma / 中国医学影像学杂志

Purpose To investigate the ultrasound imaging characteristics of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma(Xp11.2/TFE3-tRCC).Materials and Methods A retrospective analysis was conducted of 10 patients with pathologically confirmed Xp11.2/TFE3-tRCC who underwent surgery in West China Hospital of Sichuan University from April 2009 to February 2022.The ultrasonic images were collected and further analyzed,including tumor border,shape,internal echoes,Doppler findings,and contrast-enhanced ultrasonography findings.Results A total of 10 masses were finally included,4 of which underwent contrast-enhanced ultrasound.The ultrasonographic manifestations of Xp11.2/TFE3-tRCC showed diversity and variability,and the mass was most commonly located in the medulla(5 cases).Conventional ultrasound showed solid nodules with clear boundaries and regular shape similar to benign lesions in 6 cases,and color Doppler showed punctated blood flow signals in 5 cases.Contrast-enhanced ultrasound was more inclined to malignant tumors(3 cases),which showed uneven enhancement,mostly accompanied by peripheral uneven enhancement rings.Conclusion Xp11.2/TFE3-tRCC tends to be benign on conventional ultrasound,while contrast-enhanced ultrasound shows malignant lesions.Therefore,contrast enhanced ultrasound can serve as a potential diagnostic tool for suspected Xp11.2/TFE3-tRCC.

Clinicopathological characteristics of NTRK gene fusion-positive patients in papillary thyroid carcinoma / 临床与实验病理学杂志

Purpose To analyze the morphological charac-teristics of papillary thyroid carcinoma(PTC)patients with NTRK gene fusion in order to provide more important morpholog-ic evidences for molecular detection.Methods A retrospective collection of 790 cases PTC was conducted.Then the patients with NTRK gene fusion were selected.The histopathological fea-tures of PTC patients with NTRK gene fusion were compared with those of classical PTC.Results Nine cases(1.1%)of NTRK fusion positive PTC were detected,including 2 cases of NTRK1 and 7 cases of NTRK3 gene fusion.The main his-topathological features were follicular subtypes,with tumors ex-hibiting multinodular infiltration or"jumping"infiltration.The cytoplasm was associated with hyaline change.The cell morphol-ogy was slight irregularity.Conclusion The incidence of NTRK fusion is low in PTC and it tends to occur in the young group.Follicular subtype is the main characteristic histopatholo-gy,with mild tumor cells.But the ability of the invasion and metastasis is strong.Therefore,NGS detection should be per-formed for early intervention and prolonging the survival of PTC patients.

Comparative study of four technology platforms for detection of thyroid carcinoma NTRK fusion gene / 临床与实验病理学杂志

Purpose To study the consistency of NTRK fu-sion gene in the thyroid carcinoma detected by four technology platforms:immunohistochemistry,DNA-based NGS,FISH and qRT-PCR.Methods NTRK fusion gene was detected by FISH,immunohistochemical(IHC),DNA-based NGS and qRT-PCR in a same group of 40 clinical cases(among them,31 cases were thyroid cancer samples).Results In a group of 31 thyroid cancer cases detected by four techniques,compared with FISH,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and total coincidence rate(TCR)of IHC was 100%(9/9),90.9%(20/22),81.8%(9/11),100%(20/20),93.5%(29/31),respectively.The PPV of IHC was poor.The sensitivity,specificity,PPV,NPV and TCR of DNA-based NGS was 44.4%(4/9),100%(22/22),100%(4/4),81.5%(22/27),83.9%(26/31),respectively,and the sensitivity was poor.The TCR of qRT-PCR was 100%(31/31).Compared with FISH,Kappa value of IHC,DNA-based NGS and qRT-PCR was 0.853,0.532 and 1.000,respectively.Of the 40 clinical cases,the concordance between qRT-PCR and FISH was observed for 39 samples,for the qRT-PCR assay did not cover the NTRK fusion type(LM-NA:exon4-NTRK1:exon10).Compared with FISH,the coinci-dence rate of qRT-PCR was highest.Conclusion The RNA-based assay of qRT-PCR does have the advantages of high sensi-tivity and high specificity,and may be an optimal scheme for routine clinical detection of NTRK fusion variation in thyroid cancer in pathology department.

Update of international guidelines leads the clinical diagnosis and treatment of hematological malignancies into the era of precision medicine and genomics / 中华检验医学杂志

As medical research progresses, an increasing number of genetic variations are being incorporated into international guidelines for the diagnosis and treatment of hematological malignancies. In several international guidelines updated in 2022, more emphasis is placed on the importance of genetic variation in the classification and prognosis assessment of hematological malignancies. The clinical diagnosis and treatment of hematological malignancies have entered the era of precision medicine and genomics, relying increasingly on the application of high-throughput sequencing technology.

Current status of targeted therapy for cholangiocarcinoma / 国际外科学杂志

Cholangiocarcinoma is a group of highly invasive and heterogeneous biliary malignancies originating from any part of the biliary tree. At present, the most ideal treatment is still radical surgery.Gemcitabine combined with cisplatin (gem-cis) has been recognized as the standard first-line chemotherapy regimen for patients with unresectable, advanced or metastatic disease.In recent years, with the proposal of precision medicine and the development of next-generation sequencing technologies, A large number of important cholangiocarcinoma targets have been discovered, such as FGFR, IDH, VEGFR, BRAF, MET, etc., and the research on corresponding target drugs is booming.By referring to relevant literature and data, combined with domestic and foreign clinical trials, this paper reviews the important targets of cholangiocarcinoma and the latest progress of targeted drug therapy.

Clinical value of marker genes in the diagnosis of salivary gland mammary secretory carcinoma / 中华内分泌外科杂志

Objective:To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of mammary analogue secretary carcinoma of salivary gland (MASC) .Methods:From Jan. 2018 to Jan. 2021, 28 cases of salivary gland MASC were collected in Ningbo Diagnostic Pathology Center, and 10 cases of acinar cell carcinoma and 10 cases of adenoid cystic carcinoma were selected as controls. Immunohistochemical envision method was used to detect the expression of S-100,, DOG-1, CD117, SOX-10, Mammaglobin and Vimentin, and fluorescence in situ hybridization was used to detect the fusion gene of ETV6-NTRK3.Results:The S-100 protein, SOX-10 and Vimentin of MASC of salivary gland were diffusingly positive (28/28) , Mammaglobin (22/28) and CD117 (19/28) were partially positive, and DOG-1 was negative. ETV6-NTRK3 fusion transcription was successfully detected in 26 of 28 salivary gland MASC cases, of which 23 were positive and 3 were negative.Conclusions:Salivary gland MASC is a low-grade malignant epithelium tumor. Comprehensive detection of the expression levels of S-100 protein, SOX-10, DOG-1, Mammaglobin and CD117 is of great value for the diagnosis and differential diagnosis of MASC. FISH detection of ETV6-NTRK3 gene fusion has important reference value for definite diagnosis.

Imaging features of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: comparison with chromophobe renal cell carcinoma / 中华放射学杂志

Objective:To compare the imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) with chromophobe RCC.Methods:From November 2016 to January 2020, 28 patients with Xp11.2 RCC and 28 patients with chromophobe RCC confirmed by pathology were retrospectively analyzed in Peking University First Hospital. All 23 patients underwent preoperative CT examination, and 5 patients underwent routine MRI in each group. The clinical and imaging features were observed and recorded. The CT features including side, location, size, boundary, shape, uniform density, composition (solid, cystic-solid, cystic), hemorrhage, calcification, lymph node metastasis of the lesions and distant metastasis were observed, and the CT value of the solid part of the tumor at each stage was measured. On MRI images, the signal of the lesion in each sequence and enhancement mode were observed. The differences in clinical and imaging characteristics between the 2 groups were compared using independent samples t test or χ 2 test. Results:The Xp11.2 RCC more frequently affected young [(27±10) years] patients, while chromophobe RCC more frequently involved middle-aged [(37±7) years] patients asymptomatically, and the difference was statistically significant ( t=-4.99, P<0.001). The lesion size of Xp11.2 RCC [(5.4±2.2) cm] were significantly smaller than that of chromophobe RCC [(6.9±1.8) cm] ( t=-2.93, P=0.005). There were significant differences in the density and composition of lesions between Xp11.2 RCC and chromophobe RCC (χ 2=4.60, 18.67, P=0.032,<0.001). There were no significant differences in the side, location, boundary, shape, hemorrhage, calcification, fat, lymph node metastasis and distant metastasis between the 2 kind of lesions (all P>0.05). The CT values of solid components in Xp11.2 RCC in cortico-medullary phase and delayed phase were higher than those in chromophobe RCC, and the difference were statistically significant ( t=11.80, 20.15, both P<0.001). Five cases of Xp11.2 RCC showed iso- or slightly hyperintense signal on T 1WI and slightly hypointense signal on T 2WI. Two cases showed delayed enhancement after enhancement, and 3 cases showed a slight decrease in delayed phase enhancement. Conclusion:Compared with chromophobe RCC, Xp11.2 RCC has certain characteristics in imaging manifestations (lesion size, density uniformity, composition, CT value of post-enhanced cortico-medullary phase and delayed phase). Imaging manifestations combining the clinical manifestations (age of onset) are helpful for preoperative diagnosis of Xp11.2 RCC.

Development of an LB cloning system and its application in expression of fusion genes in Sphingomonas sp. WG / 生物工程学报

In order to overcome the challenges of insufficient restriction enzyme sites, and construct a fusion-expression vector with flexible fusion direction, we designed an LB cloning system based on the type IIS and type IIT restriction enzymes LguⅠ and BbvCⅠ. The LB cloning system is constructed by inserting the LB fragment (GCTCTTCCTCAGC) into the multiple cloning site region of the broad-host plasmid pBBR1MCS-3 using PCR. The LB fragment contains partially overlapped recognition sites of LguⅠ and BbvCⅠ. Therefore, the same non-palindromic sequence will be generated by these two restriction endonucleases digestion. This feature can be used to quickly and flexibly insert multiple genes into the expression vector in a stepwise and directed way. In order to verify the efficacy of the cloning system, two glycosyltransferase genes welB and welK of Sphingomonas sp. WG were consecutively fused to the LB cloning vector, and the recombinant plasmid was transferred into Sphingomonas sp. WG by triparental mating. The results showed that gene fusion expression has little effect on sphingan titer, but enhanced the viscosity of sphingan. The viscosity of the sphingan produced by recombinant strain Sphingomonas sp. WG/pBBR1MCS-3-LB-welKB was 24.7% higher than that of the wild strain after fermentation for 84 h, which would be beneficial for its application. In conclusion, the application of LB cloning system were verified using Sphingomonas sp. WG. The LB cloning system may provide an efficient tool for fusion expression of target genes.

Molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.

Acute myeloid leukemia with positive TLS-ERG fusion gene: report of 9 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Clinicopathological analysis of children with Xp11.2 translocation/ TFE3 gene fusion associated renal cell carcinoma / 中华实用儿科临床杂志

Objective:To summary the problems that may be encountered in the diagnosis of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinomas (Xp11 RCC) and to improve the understanding and diagnostic level.Methods:The clinical and pathological data of 5 children with Xp11 RCC pathologically diagnosed in Children′s Hospital of Capital Institute of Pediatrics from January 2015 to December 2019 were collected for retrospective analysis.Results:The 5 cases included 2 males and 3 females with the age of 4-8 years old.All cases presented with abdominal mass.Four cases received radical nephrectomy and radical tumor resection, and 1 case received simple tumor resection after related examination.Routine HE staining, immunohistochemical staining and fluorescence in situ hybridi-zation (FISH) were performed after surgery.The histological morphology of tumor was varied, and the tumor cells were arranged in nest flake, acinar or papillary pattern, with abundant cytoplasm form completely transparent to eosinophilic staining (pink), and gravel-like calcification was visible.Micropapillary arranged tumor cells appeared in 1 case besides classic pattern; in another case, the tumor cells were highly eosinophilic with abundant cytoplasm and visible round or elliptic eosinophilic bodies.The tumor cells in 5 cases showed diffuse and strong expression of TFE3, and FISH assay showed abnormal separation signal.Conclusions:Xp11 RCC is a relatively rare renal malignant tumor with diverse histological morphology, which should be distinguished from other common renal tumors in children.Its immunohistochemical expression and molecular detection are of specificity, and it should be diagnosed based on clinical incidence.

Clinical characteristics and prognosis of MLL-AF6 positive patients with acute myeloid leukemia / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical features and prognosis of acute myeloid leukemia (AML) patients with the mixed lineage leukemia (MLL) gene rearrangements AF6 (MLL-AF6) positive.@*METHODS@#In the study, 11 patients who were newly diagnosed with MLL-AF6 positive AML were analyzed retrospectively, related literature was reviewed to clarify the clinical features and prognosis of MLL-AF6 positive patients.@*RESULTS@#Among the 11 patients, there were 6 males and 5 females, with a median age of 36 years. Six patients were diagnosed with AML M5 and five with M4 according to FAB classification (French-American-British classification systems). Gingival swelling and pain occurred in 6 cases and fever occurred in 5 cases. At first diagnosis, the median white blood cells were 55.5×109/L. Immunotype showed the expression of myeloid/monocyte and early stem cell series antigens. The expression level of MLL-AF6 fusion gene (real-time quantitative PCR) was 14.2%-214.5%, and 6/11 cases (54.5%) were associated with high EVI1 gene expression. Mutations of KRAS, TET2, ASXL1, TP53, DNMT3A, and FLT3-ITD were detected by next generation sequencing (NGS) in 4 patients. Chromosome G banding examination showed that 2 cases were t(6;11)(q27, q23) with complex karyotype abnormality, 4 cases with +8 abnormality and 2 cases with normal karyotype. Hematological complete remission (CR) was achieved in 8/11 patients (72.7%) after conventional induction chemotherapy, and primary drug resistance was observed in 3 patients. Two of the eight patients with CR were negative for minimal residual disease (MRD), with a median CR duration of 4.5 months. Two patients with positive MRD and three patients with refractory recurrence underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), but all died due to leukemia progression. At the end of follow-up on December 1, 2019, 2 patients were alive and 9 died, with median survival time of 9 months.@*CONCLUSION@#The AML patients with MLL-AF6 positive were mostly young, the majority of FAB types were M4 and M5, and most of the patients often had fever as the first symptom, with increased white blood cells, accompanied by organ infiltration, and high EVI1 gene expression. The hematological remission rate of routine chemotherapy is not low, but it is difficult to achieve molecular remission, most of which have early recurrence. Early allo-HSCT in a molecular negative state may prolong the CR duration.

Research progress on MiT family translocation related renal cell carcinoma / 中华泌尿外科杂志

Microphthalmia-associated transcription (MiT) family translocation related renal cell carcinoma (RCC) is an important type of renal cell carcinoma, which was included in the new classification of renal tumors by the World Health Organization (WHO) as an independent subtype in 2016. This type of renal cell carcinoma mainly includes Xp11.2 translocation /TFE3 gene fusions associated with renal cell carcinoma and T (6; 11)(p21; q12)/TFEB gene fusion-associated renal cell carcinoma, which has similar clinical features, histology, immunohistochemistry, and molecular genetics, but is significantly different from other renal cell carcinomas. In this review, the clinicopathology and genetics of MiT family translocation associated renal cell carcinoma were reviewed in order to provide guidance and help to the clinical and pathologic work.

Prognostic significance of DEK-NUP214 fusion gene in patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective:To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People′s Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test.Results:The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome.Conclusion:Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.

Mammary analogue secretory carcinoma: An Indian experience of a novel entity

Aims: To explore clinical, histopathological and immunohistochemistry (IHC) features of mammary analogue secretory carcinoma (MASC) with systematic literature review. Settings and Design: Hospital based cross-sectional study. Subjects and Methods: The data of all cases of MASC diagnosed over a period of 1 year i.e., from July 2017 to July 2018 were retrieved. The haematoxylin and eosin (H and E) sections, and IHC sections were studied. A strict histological and recently updated criteria were applied and patients with a confirmed diagnosis of MASC were included in the study. A systematic literature review was conducted by searching the PubMed and National Centre for Biotechnology Information database. Statistical Analysis Used: Microsoft Excel 2010. Results: The present case series is 27th in the English literature and 1stcase series describing its histopathology in the Indian literature. The mean age of presentation is 43 years. Female preponderance was found i.e., M:F ratio of 0.5. Conclusion: Histopathology and if necessary, followed by IHC is required for the confirmation of diagnosis of MASC. We should be aware about this recently described entity which is usually mistaken for other low grade salivary gland carcinomas like Acinic cell carcinoma (AciCC) and Mucoepidermoid carcinoma (MEC). The knowledge about its typical morphology, high degree of suspicion and IHC confirmation with both S-100 and Mammaglobin help in precise diagnosis.

Gene Fusions as Acquired Resistance Mechanisms of EGFR-TKI / 中国肺癌杂志

Patients with sensitive epidermal growth factor receptor (EGFR) mutations often respond to tyrosine kinase inhibitors (TKIs), but acquired resistance will eventually develop. The most common mechanisms of acquired resistance include secondary EGFR mutation, MET amplification, and histologic transformation. Besides, gene fusions could also mediate the process of acquired resistance. Various gene fusions including rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and anaplastic lymphoma kinase (ALK) could take place after TKIs resistance, the incidence of which is around 1%. The clinical cases and experiments both in vitro and in vivo have proved the role of gene fusions in EGFR-TKI resistance. The combination of EGFR inhibitors and gene fusion inhibitors might be an effective therapeutic method. The understanding of gene fusions at EGFR-TKI resistance may contribute to the subsequent diagnosis and treatment strategy.

FusionScan: accurate prediction of fusion genes from RNA-Seq data

Identification of fusion gene is of prominent importance in cancer research field because of their potential as carcinogenic drivers. RNA sequencing (RNA-Seq) data have been the most useful source for identification of fusion transcripts. Although a number of algorithms have been developed thus far, most programs produce too many false-positives, thus making experimental confirmation almost impossible. We still lack a reliable program that achieves high precision with reasonable recall rate. Here, we present FusionScan, a highly optimized tool for predicting fusion transcripts from RNA-Seq data. We specifically search for split reads composed of intact exons at the fusion boundaries. Using 269 known fusion cases as the reference, we have implemented various mapping and filtering strategies to remove false-positives without discarding genuine fusions. In the performance test using three cell line datasets with validated fusion cases (NCI-H660, K562, and MCF-7), FusionScan outperformed other existing programs by a considerable margin, achieving the precision and recall rates of 60% and 79%, respectively. Simulation test also demonstrated that FusionScan recovered most of true positives without producing an overwhelming number of false-positives regardless of sequencing depth and read length. The computation time was comparable to other leading tools. We also provide several curative means to help users investigate the details of fusion candidates easily. We believe that FusionScan would be a reliable, efficient and convenient program for detecting fusion transcripts that meet the requirements in the clinical and experimental community. FusionScan is freely available at http://fusionscan.ewha.ac.kr/.

Clinical characteristics and prognosis analysis of childhood B‐cell acute lymphoblastic leukemia with TEL‐AML1 fusion gene positive / 白血病·淋巴瘤

Objective To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia (B-ALL) with TEL-AML1 fusion gene positive. Methods Clinical characteristics, therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Childrenˊs Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed. Kaplan-Meier method was used to evaluate 3-year event-free survival (EFS) rate and overall survival (OS) rate. Influencing factors of EFS and OS were evaluated by using Cox regression analysis. Results TEL-AML1 fusion gene was positive in all 55 children, and no other fusion gene positive was merged. There were 4 patients (7.3% ) ≥10 years old. At initial diagnosis, 33 patients (60.0% ) had hepatomegaly, 28 patients (50.9%) had splenomegaly, and 27 patients (49.1%) had superficial lymphadenectasis. There were 5 patients (9.1%) with white blood cell count≥50×109/L, and 19 patients (34.6%) had abnormalities of chromosome. All the 55 children were divided into the low risk group [36 cases (65.5%)], the intermediate risk group [18 cases (32.7%)], high risk group [1 case (1.8%)] according to Morphology, Immunology, Cytogenetics and Molecular Biology (MICM) and adjusted risk. After regular treatments, 50 patients achieved complete remission (CR) on the 15th day. The CR rate after one-course of induction therapy was 100.0%. On the 33rd day, 43 patients (78.2%) had minimal residual disease (MRD) <10-4, 12 patients (21.8%) had MRD≥10-4 and MRD<10-2, 1 patient (1.8%) had MRD≥10-3 at the 12th week. During three to six months, the negative rate of fusion gene was 61.8% (34/55). There were 3 deaths (5.5%), and one (1.8%) of them died of recurrence, and the recurrence time was 27 months from the initial diagnosis; the other 2 cases (3.6%) died of infection during chemotherapy. In 55 patients, the 3-year EFS rate and OS rate was 90.3% and 93.2%, respectively. The 3-year EFS rate and OS rate in the low risk group was 100.0% both; the 3-year EFS rate and OS rate in the intermediate risk group was 78.7% and 86.6%, respectively; the 3-year EFS rate and OS rate in the high risk group was 0 both and one died. EFS rate and OS rate in low risk group were higher than those in the intermediate risk group, and the differences were statistically significant (P< 0.05). The EFS rate was 92.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group, and OS rate was 95.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group (P<0.05). Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS ( OR＝2.971, 95% CI 1.330-6.633, P＝0.008; OR＝2.884, 95% CI 1.295-6.419, P＝0.009). Conclusions Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate, high survival rate and good prognosis. Risk stratification and the 12th week MRD are the influencing factors of the prognosis.

Acute myeloid leukemia with FIP1‐like‐1‐platelet‐derived growth factor receptor α fusion gene positive progressed from idiopathic hypereosinophilic syndrome: report of one case and review of literature / 白血病·淋巴瘤

Objective To improve the understanding of idiopathic hypereosinophilic syndrome (HES) and to be aware of its potential of transforming to acute myeloid leukemia (AML). Methods The clinical data of one patient diagnosed with HES progressed to AML in the 923rd Hospital of the Peopleˊs Liberation Army Joint Service Support Force were analyzed, and relevant literatures were reviewed. Results The patient was diagnosed with idiopathic HES that progressed to AML with FIP1-like-1-platelet-derived growth factor receptor α (FIP1L1-PDGFRA) after 2 years. The patients achieved complete remission after the treatment of chemotherapy combined with tyrosine kinase inhibitor and then received hematopoietic stem cell transplantation. The patient had more than 1 year disease-free survival until the deadline. Conclusion Idiopathic HES has the potential to transform to AML with FIP1L1-PDGFRA fusion gene positive, therefore regular follow-up should be emphasized.

Clinical characteristics and prognosis analysis of childhood B-cell acute lymphoblastic leukemia with TEL-AML1 fusion gene positive / 白血病·淋巴瘤

Objective@#To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia (B-ALL) with TEL-AML1 fusion gene positive.@*Methods@#Clinical characteristics, therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Children's Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed. Kaplan-Meier method was used to evaluate 3-year event-free survival (EFS) rate and overall survival (OS) rate. Influencing factors of EFS and OS were evaluated by using Cox regression analysis.@*Results@#TEL-AML1 fusion gene was positive in all 55 children, and no other fusion gene positive was merged. There were 4 patients (7.3%) ≥10 years old. At initial diagnosis, 33 patients (60.0%) had hepatomegaly, 28 patients (50.9%) had splenomegaly, and 27 patients (49.1%) had superficial lymphadenectasis. There were 5 patients (9.1%) with white blood cell count ≥50×109/L, and 19 patients (34.6%) had abnormalities of chromosome. All the 55 children were divided into the low risk group [36 cases (65.5%)], the intermediate risk group [18 cases(32.7%)], high risk group [1 case (1.8%)] according to Morphology, Immunology, Cytogenetics and Molecular Biology (MICM) and adjusted risk. After regular treatments, 50 patients achieved complete remission (CR) on the 15th day. The CR rate after one-course of induction therapy was 100.0%. On the 33rd day, 43 patients (78.2%) had minimal residual disease (MRD) <10-4, 12 patients (21.8%) had MRD≥10-4 and MRD<10-2, 1 patient (1.8%) had MRD≥10-3 at the 12th week. During three to six months, the negative rate of fusion gene was 61.8% (34/55). There were 3 deaths (5.5%), and one (1.8%) of them died of recurrence, and the recurrence time was 27 months from the initial diagnosis; the other 2 cases (3.6%) died of infection during chemotherapy. In 55 patients, the 3-year EFS rate and OS rate was 90.3% and 93.2%, respectively. The 3-year EFS rate and OS rate in the low risk group was 100.0% both; the 3-year EFS rate and OS rate in the intermediate risk group was 78.7% and 86.6%, respectively; the 3-year EFS rate and OS rate in the high risk group was 0 both and one died. EFS rate and OS rate in low risk group were higher than those in the intermediate risk group, and the differences were statistically significant (P < 0.05). The EFS rate was 92.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group, and OS rate was 95.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group (P < 0.05). Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS (OR= 2.971, 95% CI 1.330-6.633, P= 0.008; OR= 2.884, 95% CI 1.295-6.419, P= 0.009).@*Conclusions@#Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate, high survival rate and good prognosis. Risk stratification and the 12th week MRD are the influencing factors of the prognosis.