Objective:To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria).Methods:In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results:Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs. 4.3% (10/232), 14.3% (4/28) vs. 3.9% (9/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1 ,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33, P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49 ,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44 , P=0.119). Conclusions:Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Objective:To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse ( HR=3.91, 95% CI 1.96-7.79; HR=4.15, 95% CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse ( HR=6.50, 95% CI 2.58-16.34; HR=5.19, 95% CI 1.78-15.16), with ETV6::RUNX1 ( HR=0.23, 95% CI 0.07-0.74) and HSCT after relapse ( HR=0.24, 95% CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions:Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

Objective:To evaluate the role of Jumonji domain-containing 3 (JMJD3) in cisplatin-induced renal fibrosis following acute kidney injury in mice.Methods:Forty-eight healthy C57BL/6 male mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (group CON), control plus JMJD3 inhibitor group (group CON-A), cisplatin group (group CIS), and cisplatin plus JMJD3 inhibitor group (group CIS-A). In group CIS and group CIS-A, cisplatin was intraperitoneally administered on 1st and 14th days, respectively, to develop a renal fibrosis model in mice with acute kidney injury, and the JMJD3 inhibitor GSKJ4 10 mg/kg and equal volume of PBS were intraperitoneally injected on 4th day, respectively, once every 3 days, 6 injections in total.The equal volume of PBS and GSKJ4 10 mg/kg were intraperitoneally injected at the corresponding time points in group CON and group CON-A, respectively.Six mice in each group were selected, and orbital blood samples were collected on 3rd day after the first injection of cisplatin to determine the concentrations of serum creatinine (Cr) and blood urea nitrogen (BUN), then the animals were sacrificed, and kidney tissues were obtained for microscopic examination of pathological changes after HE and PAS staining (with a light microscope), and the damage to kidneys was assessed and scored.Six mice were sacrificed on 28th day after the first injection of cisplatin, and kidney tissues were removed for determination of the area of renal fibrosis ( via Sirius red and Masson staining), expression of fibronectin (Fn), collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) (by immunofluorescence), F4/80 + cell and CD3 + cell count (using immunohistochemical method), and expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), CXC chemokine ligand 16 (CXCL16), and monocyte chemoattractant protein1 (MCP-1) mRNA (by real-time polymerase chain reaction). Results:Compared with group CON, the serum BUN and Cr concentrations, renal injury scores, and area of renal fibrosis were significantly increased, the expression of Fn, Col Ⅰ and α-SMA was up-regulated, the F4/80 + cell and CD3 + cell count was increased, and the expression of IL-6, CXCL16, TNF-α and MCP-1 mRNA was up-regulated in group CIS ( P<0.05), and no significant change was found in the parameters mentioned above in group CON-A ( P>0.05). Compared with group CON-A, the serum BUN and Cr concentrations, renal injury scores, and area of renal fibrosis were significantly increased, the expression of Fn, Col Ⅰ and α-SMA was up-regulated, the F4/80 + cell and CD3 + cell count was increased, and the expression of IL-6, CXCL16, TNF-α and MCP-1 mRNA was up-regulated in group CIS-A ( P<0.05). Compared with group CIS, the serum BUN and Cr concentrations, renal injury scores, and area of renal fibrosis were significantly decreased, the expression of Fn, Col Ⅰ and α-SMA was down-regulated, the F4/80 + cell and CD3 + cell count was decreased, and the expression of IL-6, CXCL16, TNF-α and MCP-1 mRNA was down-regulated in group CIS-A ( P<0.05). Conclusions:JMJD3 is involved in the process of renal fibrosis following acute kidney injury in mice, and the mechanism may be related to promotion of inflammatory responses.

Objective:To evaluate the role of natural killer T cells in renal fibrosis in mice with acute kidney injury (AKI).Methods:Twenty-four clean-grade healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), AKI group (group A), control plus CD1d antibody group (group C-MA), and AKI plus CD1d antibody group (group A-MA). The model of renal fibrosis in mice with AKI was established by intraperitoneal injection of folic acid 250 mg/kg.In group C, homotypic control antibody 20 mg/kg was injected via the tail vein.In group AKI, homotypic control antibody 20 mg/kg was injected via the tail vein at 24 h before establishing the model. In group C-MA, anti-CD1d monoclonal antibody 20 mg/kg was injected via the tail vein.In group A-MA, anti-CD1d monoclonal antibody 20 mg/kg was injected via the tail vein at 24 h before establishing the model.On the 14th day after folic acid injection, blood samples were taken from eyeballs to determine the concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in serum.Then the mice were sacrificed, and the renal tissues were taken for Sirius red staining and HE staining to determine the area of renal fibrosis, and renal injury was scored.The expression of fibronectin (FN), type I collagen (Col-Ⅰ) and alpha-smooth muscle actin (α-SMA) in renal tissues was detected by immunofluorescence method.The expression of interleukin (IL)-4, IL-13, arginase-1 (Arg-1) and found in inflammatory zone 1 (FIZZ1) mRNA in renal tissues was detected by real-time polymerase chain reaction. Results:Compared with group C, the concentrations of BUN and Cr in serum, renal injury score, and area of renal fibrosis were significantly increased, the expression of FN, Col-Ⅰ and α-SMA and IL-4, IL-13, Arg-1 and FIZZ1 mRNA was up-regulated in A and A-MA groups ( P<0.05), and no significant change was found in the above indexes in group C-MA ( P>0.05). Compared with group A, the concentrations of BUN and Cr in serum, renal injury score, and area of renal fibrosis were significantly decreased, the expression of FN, Col-Ⅰ and α-SMA and IL-4, IL-13, Arg-1 and FIZZ1 mRNA was down-regulated in group A-MA ( P<0.05). Conclusion:Activation of natural killer T cells is involved in the process of renal fibrosis in mice with AKI, and the mechanism may be related to promoting the release of Th2 cytokines and M2 polarization of macrophages.

Objective:To evaluate the role of CXC chemokine receptor 6 (CXCR6)-mediated activation of natural killer T (NKT) cells in renal fibrosis following acute kidney injury (AKI) in mice.Methods:Eighteen male wild-type C57BL/6 mice and 18 CXCR6 knockout C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 6 groups ( n=6 each) using a random number table method: wild-type mouse control group (group WT-CON), CXCR6 knockout mouse control group (group CXCR6 -/--CON), wild-type mouse with AKI group (group WT-AKI), CXCR6 knockout mouse with AKI group (group CXCR6 -/--AKI), wild-type mouse with AKI + NKT cell adoptive transfer group (group WT-AKI-NKT) and CXCR6 knockout mouse with AKI + NKT cell adoptive transfer group (group CXCR6 -/--AKI-NKT). Folic acid 250 mg/kg was intraperitoneally injected to establish the model of renal fibrosis in mice with AKI.NKT cellsuspension 250 μl(1×10 6 cells) was injected through the tail vein on the 4th and 9th days after folic acid injection in group WT-AKI-NKT and group CXCR6 -/--AKI-NKT, respectively.Blood samples were taken from orbital at day 14 after folic acid injection for determination of the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr). The animals were sacrificed, and renal tissues were obtained for observation of the area of renal fibrosis (by Sirius red staining) and renal injury (using H&E staining) which was scored and for determination of the proportion of CD1d Tetramer+ cells (by flow cytometry), the number of CD206 and α-smooth muscle actin (α-SMA) double positive (CD206 + -α-SMA + ) cells (by immunofluorescence) and expression of interleukin (IL)-4 and IL-13 mRNA (by real-time polymerase chain reaction). Results:Compared with group WT-CON, the BUN and Cr levels, renal injury scores, area of renal fibrosis, proportion of CD1d Tetramer + cells and CD206 + -α-SMA + cell count were significantly increased, and the expression of IL-4 and IL-13 mRNA was up-regulated in group WT-AKI and WT-AKI-NKT ( P<0.05). Compared with group WT-AKI, the BUN and Cr levels, renal injury scores, area of renal fibrosis, proportion of CD1d Tetramer + cells and CD206 + -α-SMA + cell count were significantly increased, and the expression of IL-4 and IL-13 mRNA was up-regulated in group WT-AKI-NKT ( P<0.05), and the BUN and Cr levels, renal injury scores, area of renal fibrosis, proportion of CD1d Tetramer + cells and CD206 + -α-SMA + cell count were significantly decreased, and the expression of IL-4 and IL-13 mRNA was down-regulated in group CXCR6 -/--AKI ( P<0.05). Compared with group CXCR6 -/--CON, the BUN and Cr levels, renal injury scores, area of renal fibrosis, proportion of CD1d Tetramer + cells and CD206 + -α-SMA + cell count were significantly increased in group CXCR6 -/--AKI and group CXCR6 -/--AKI-NKT ( P<0.05). Compared with group CXCR6 -/--AKI, the BUN and Cr levels, renal injury scores, area of renal fibrosis, proportion of CD1d Tetramer + cells and CD206 + -α-SMA + cell count were significantly increased, and the expression of IL-4 and IL-13 mRNA was up-regulated in group CXCR6 -/--AKI-NKT ( P<0.05). Conclusion:CXCR6-mediated activation of NKT cells is involved in renal fibrosis following AKI in mice, and the mechanism may be related to promoting Th2 cytokine-mediated M2 macrophage-myofibroblast transformation.

Objective:To evaluate the role of interleukin-4 (IL-4) in renal fibrosis induced by acute kidney injury (AKI) in mice.Methods:Twenty-four male C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups ( n =6 each) using a random number table method: control group (group CON), AKI group, control plus anti-IL-4 antibody group (group CON-A), and AKI plus anti-IL-4 antibody group (group AKI-A). In AKI-A and AKI groups, folic acid was intraperitoneally injected to induce AKI in anesthetized mice, and the anti-IL-4 antibody 40 mg/kg and the equal volume of PBS were intraperitoneally injected, respectively, at 3, 6, 9 and 12 days after injection. The equal volume of PBS and anti-IL-4 antibody was given at the corresponding time point in CON and CON-A groups, respectively.The orbital blood samples were taken on day 14 after injecting folic acid for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were then sacrificed, and renal tissues were obtained for examination of the pathological changes (using Sirius red staining and Masson staining) and for determination of the expression of fibronectin(FN), collagen-Ⅰ(Col-Ⅰ) and α-smooth muscle actin (α-SMA) (by Western blot) and expression of CD206, Arg-1 and FIZZ1 mRNA (by real-time polymerase chain reaction). The area of renal fibrosis was measured. Results:Compared with group CON, the serum BUN and Cr concentrations were significantly increased, the area of renal fibrosis was increased, and the expression of FN, Col-Ⅰ, α-SMA and CD206, Arg-1 and FIZZ1 mRNA in renal tissues was up-regulated in group AKI ( P<0.05), and no significant change was found in the parameters mentioned above in group CON-A( P>0.05). Compared with group AKI, the serum BUN and Cr concentrations were significantly decreased, the area of renal fibrosis was reduced, and the expression of FN, Col-Ⅰ, α-SMA and CD206, Arg-1 and FIZZ1 mRNA in renal tissues was down-regulated in group AKI-A ( P<0.05). Conclusion:IL-4 is involved in the process of renal fibrosis following AKI, and the mechanism may be associated with the regulation of macrophage M2 polarization in mice.

Objective: To evaluate the effect of plasma exchange combined with high-dose continuous venovenous hemodiafiltration method (CVVHDF) in the treatment of patients with acute-on-chronic liver failure with stage III-IV hepatic encephalopathy and the feasibility of pre-operative preparation for liver transplantation. Methods: Clinical data of 14 cases of medical intensive care unit of our hospital with acute-on- chronic liver failure accompanied with stage III-IV hepatic encephalopathy that underwent plasma exchange combined with high-dose CVVHDF from March 2015 to September 2017 were retrospectively summarized. The indexes of liver and kidney function, blood coagulation function, arterial blood PH, lactic acid and blood ammonia were monitored before and after treatment. Heart rate, blood pressure, APACHE II score, and consciousness recovery time were observed. Student’s t- test was used to compare the mean values between the two groups. Results: Serum total bilirubin (t = 9.43, P < 0.01), serum creatinine (t = 3.40, P < 0.01), serum ammonia (t = 10.64, P < 0.01), prothrombin activity (t = 9.19, P < 0.01), serum lactate (t = 9.25, P < 0.01), heart rate (t = 4.47, P < 0.01), and mean arterial pressure (t = 4.41, P < 0.05) were significantly improved in 14 patients before and after treatment. In addition, respiratory rate (t = 6.01, P < 0.01) and APACHE II score (t = 7.19, P < 0.01) were significantly improved (P < 0.05). Eight patients with stage III hepatic encephalopathy were treated with intermittent plasma exchange combined with CVVHDF for 3 to 14 days, and six patients with stage IV were transformed to stage III to II. Liver transplantation was successfully performed on 14 patients with shortest time duration of 3days, and longest time duration of 1 month. Conclusion Plasma exchange combined with CVVHDF can significantly improve liver and kidney functions, reduce blood ammonia level and improve mental health in patients with hepatic failure accompanied with stage III-IV hepatic coma. In addition, it also effectively increases the average arterial pressure, maintain stability of vital signs, maintain fluids, electrolytes and acid-base balance, create a stable internal environment for liver transplantation before operation, and extend time for liver transplantation.

Objective: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1⁺ acute lymphoblastic leukemia (ALL) in China. Methods: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1⁺ ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) . Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1⁺ ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome. Conclusion The clone evolution was detected in pediatric ETV6-RUNX1⁺ ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.

OBJECTIVETo evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis.

METHODTotally 141 children (<14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA). The survival rate between the patients with CNVs were explored. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared with the log-rank test.

RESULTAmong the 141 cases, 55.3% (n=78) were boys and 44.7% (n=63) were girls and the median age was 4 (1-13) years. The estimated 5-year DFS rate for the patients was (84±4)%. The estimated 5-year OS rate for the patients was (85±4)%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases (76.8%). CNVs of genes EBF1(15.8%), CDKN2A/2B(18.9%), PAX5(21.1%), ETV6(54.8%), BTG1(10.5%) were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival (RFS) was statistically significant among 3 groups (χ(2)=9.809, P=0.007) . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups(χ(2)=7.622, P=0.022). ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups (χ(2)=11.045, P=0.004).

CONCLUSIONThe CNVs had prognostic relevance in ETV6/RUNX1 positive ALL.

Adolescent ; Child ; Core Binding Factor Alpha 2 Subunit ; DNA Copy Number Variations ; Disease-Free Survival ; Humans ; Multiplex Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Proto-Oncogene Proteins c-ets ; Repressor Proteins ; Survival Rate