Prognostic analysis of children with Philadelphia chromosome-like acute lymphoblastic leukemia common genes / 中华儿科杂志

Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ2 test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×109/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ2=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ2=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.

Screening Serum Differential Proteins in Children with Acute Promyelocytic Leukemia Based on iTRAQ Technique / 中国实验血液学杂志

OBJECTIVE@#To screen the serum differentially expressed proteins of APL in children.@*METHODS@#Serum protein expression profiles from 20 cases of normal healthy controls, and 20 cases of APL patients were detected by iTRAQ (isobaric tag for relative and absolute quantification)labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry(2DLC-MS/MS), and analyzed by bioinformatics software. S100A8, LRG1 and SPARC were validated by ELISA. ROC was built by SPSS 20.0 software.@*RESULTS@#Analysis identified 83 differentially expressed proteins in APL serum compared with control according to our defined criteria, of which 33 proteins were up-regulated and 50 proteins were down-regulated (P<0.05)．IPA analysis revealed that these differentially expressed proteins were related to the function of Cellular Movement, Immune Cell Trafficking, Hematological System Development and Function, Cell-To-Cell Signaling and Interaction, Tissue Development, and involved in a variety of signalling Pathways, the most representative pathways including LXR/RXR Activation and Acute Phase Response Signaling. S100A8 and LRG1 were found to be elevated and SPARC was markedly down-regulated in serum of childhood APL when compared to the normal controls as examined by ELISA (P<0.05), which was consistent with the iTRAQ result. The overall predictive accuracy of each protein was reflected by the area under the ROC curve(AUC), S100A8,LRG1 and SPARC with ROC areas of 0.841,1.000 and 0.944 respectively.@*CONCLUSION@#S100A8,LRG1 and SPARC may be serve as serum candidate biomarkers for pediatric APL.

Expression and Clinical Significance of C/EBPα Gene in Elderly Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of C/EBPα gene in elderly patients with multiple myeloma （MM） and its prognostic significance.@*METHODS@#Sixty-nine olderly patients with multiple myeloma (MM) treated in our hospital from February 2015 to October 2017 were selected and enrolled in the MM group, 38 healthy persons received physical examination were selected and enrolled in the control group. The bone marrow of 2 groups was collected and the mononuclear cells were isolated.The mRNA expression level of C/EBPα gene in mononuclear cells was determined by RT-PCR, the Western blot was used to detect the protin expression level of PBMNC C/EBPα, and the protein level of C/EBPα in bone marrow was detected by immunohistochemistry. The correlations of C/EBPα gene expression with the clinical characteristics and survival time in MM patients were analyzed.@*RESULTS@#The expression level of mRNA and protein of C/EBPα in MM patients was significantly lower than that in the control group (P0.05).Immunohistochemical staining showed that the bone marrow samples of the control group were stained more deeply, and the staining intensity in bone marrow samples of MM patients with CR, PR and relapse was successively descended. The protein level of C/EBPα in CR patients with MM was significantly higher than that in PR and relapsed patients by Western blot (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in the patients with high expression of C/EBPα gene were higher than those in low expression group (P<0.05). Multivariate Cox regression analysis showed that CRP,ratio of myeloma cells and C/EBPα gene were independent factors affecting OS and PFS (P<0.05).@*CONCLUSION@#The expression level of C/EBPα gene in MM patients is low that may stimulate the genesis of MM, and the expression of C/EBPα gene closely relates with the development of MM disease.

ITRAQ Coupled with 2DLC-MS/MS to Screen and Identify Speci-fic Bio-markers of T-Cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To screen and identify potential biomarkers specific for T-cell acute lymphoblastic leukemia (T-ALL).</p><p><b>METHODS</b>Sera were collected from 20 newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients and 20 T-ALL patients. Proteins were extracted, purified and digested with trypsin. All specimens were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) in a data-dependent mode. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression of serum soluble L-selectin (sL-selectin).</p><p><b>RESULTS</b>A total of 468 proteins were identified from distinct peptides. Compared with B-ALL group, 31 proteins were significantly differentially up-regulated while 7 proteins were significantly down-regulated in T-ALL group, sL-selectin was the higher up-regulated in these differential expression proteins. The overexpression of sL-selectin in T-ALL was verified by ELISA.</p><p><b>CONCLUSION</b>There are the differentially expressed proteins between T-ALL and B-ALL, and the sL-selectin is specific for T-ALL, which can not only become a new biomarker for the diagnosis and prognosis of T-ALL, but also can be used as a potential target for therapy of this leukemia.</p>

The inhibition effect of DFO alone and in combination with ATO on xenograft tumor growth of HL-60 cells in nude mice and its possible mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of deferoxamine (DFO) and DFO in combination with arsenic trioxide (ATO) on inhibition of HL-60 cells xenograft tumor growth in nude mice and its mechanism.</p><p><b>METHODS</b>Xenograft tumor model of HL-60 cell line in nude mice was established by inoculating HL-60 cells subcutaneously into nude mice. The tumor-bearing mice were randomly divided into four groups: 50 mg/kg DFO group (group I), 3 mg/kg ATO group (group II), combination group (50 mg/kg DFO + 1.5 mg/kg ATO (group III) and normal saline control group. The drugs were administered intraperitoneally from the day of inoculation (once a day for 10 days). The inhibitory effects on the tumor growth were compared. NF-κBp65 expression levels of the tumors were detected by immunohistochemistry (24h after the last administration).</p><p><b>RESULTS</b>(1) Tumors growth could be observed in all of the nude mice on day 7 to day 8 after inoculation, 0.5 - 1.0 cm in diameter, and then grew rapidly; (2) Tumor weight of control group, group I, group II and group III were (2.62 ± 0.54) g, (2.55 ± 0.82) g, (2.34 ± 0.79) g and (1.95 ± 0.39) g respectively, and the growth inhibition rates in group I, group II and group III were 2.67%, 10.69% and 25.57% respectively. Both DFO alone and in combination with ATO could inhibit the growth of transplanted tumors, and the combination group exhibited more effects, with no vital organ damages in the tumor-bearing mice. (3) There was significant difference in mean value of NF-κBp65 expression among the three experimental groups (P < 0.05), with a descending order of control group > group II, > group I > group III.</p><p><b>CONCLUSION</b>(1) Both DFO and ATO have antitumor activities on tumor-bearing mice, and their combination has an obvious and significant effect. (2) DFO combined with ATO, is well tolerated with no significant adverse effects in the nude mice. (3) Both DFO and ATO can downregulate NF-κBp65 expression of transplanted tumors, especially for their combination.</p>

Role of Serum Ferritin on Diagnosis and Evaluation of Therapeutic Effect of Hemophagocytic Lymphohistiocytosis in Children / 实用儿科临床杂志

1 000 ?g?L-1.The levels of SF in HLH group were much higher than those in healthy control group(P0.05).3.Seven cases with CR recurrenced.The levels of SF increased again when recurrence,which were significantly different with those of CR(P