2.Mutation and expression of PAX5 gene in adult acute lymphoblastic leukemia.
Zhong-Kun LIN ; Run ZHANG ; Zheng GE ; Jing-Yan XU ; Juan LIU ; Xing GUO ; Min LI ; Yu-Jie WU ; Chun QIAO ; Hai-Rong QIU ; Jian-Fu ZHANG ; Jian-Yong LI
Journal of Experimental Hematology 2014;22(5):1206-1211
PAX5 is an important transcription factor of paired-box(PAX) family. The aim of this study was to investigate the mutations and expression of PAX5 and its clinical significance in adult patients with acute lymphoblastic leukemia (ALL). Reverse transcription polymerase chain reaction (RT-PCR) and genomic PCR were performed to detect the deletions of PAX5 and point mutations of PAX5 exon 2-10 in 101 cases of adult ALL and were confirmed by cloning and sequencing. In addition, quantitative PCR (qPCR) was performed to evaluate the expression of PAX5. Furthermore, the correlations of mutations and expression of PAX5 with clinical parameters were analyzed, and the prognostic significance was evaluated as well. The results showed that PAX5 mutations were observed in 8 of 101 (7.9%) patients with B-ALL. A total of 9 types of mutations were detected, including 4 types of deletions, 4 types of point mutations and 1 insertion mutation; percentage of patients with age ≥ 50 years was higher in PAX5 mutation group than in wide-type group (62.5% vs 21.5%,P = 0.031) . The statistical differences were observed in B-cell subtype, initial platelet count and immunophenotypes between high and low expression of PAX5 (P < 0.05) . In addition, patients with high expression of PAX5 had higher first complete remission rate (86.7% vs 62.5%, P = 0.030) and 6-month overall survival rate (75.0% vs 50.0%, P = 0.034) compared with patients with low expression of PAX5. It is concluded that deletion/insertion/point mutations and aberrant expression of PAX5 can be observed in adult patients with B-ALL. Mutations and aberrant expression of PAX5 correlated with clinical parameters and have important clinical significance.
Adult
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Exons
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Gene Expression Regulation, Leukemic
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Humans
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Mutation
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PAX5 Transcription Factor
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genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
genetics
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Prognosis
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Sequence Deletion
3.Research progress in Ph-like childhood acute lymphoblastic leukemia.
Chinese Journal of Contemporary Pediatrics 2017;19(11):1213-1218
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subtype of B-lineage ALL (B-ALL) that displays a gene expression profile (GEP) similar to Philadelphia chromosome-positive ALL (PhALL). It has a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, frequently accompanied by abnormal transcription factors related to lymphatic development. Children with Ph-like ALL account for 15% of children with high-risk B-ALL. It has adverse clinical features and a poor prognosis. Tyrosine kinase inhibitors combined with chemotherapy can significantly improve the prognosis of children with PhALL, suggesting that targeted therapy based on the molecular cytogenetic abnormalities of Ph-like ALL has good research prospects. This paper expounds the genetic alterations, pathogenesis, clinical features, diagnostic measures, and potential therapeutic approaches of Ph-like childhood ALL based on recent research progress in Ph-like ALL.
Humans
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Janus Kinase 2
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genetics
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PAX5 Transcription Factor
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genetics
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
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diagnosis
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drug therapy
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genetics
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Proto-Oncogene Proteins c-abl
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genetics
4.Sequence analysis of 5'-flanking region of human pax-5 gene exon 1B.
Mao-Lin LIU ; Mizanur RAHMAN ; Yasuhiko HIRABAYASHI ; Takeshi SASAKI
Journal of Experimental Hematology 2002;10(2):100-103
Pax-5 gene is important transcription factor in B-lymphopoiesis and B-cell development. To understand the regulatory mechanism of pax-5 expression, the immediate 5'-flanking region (6 671 bp) of human pax-gene exon 1B was isolated and characterized. Analysis of the total sequence showed that the proximal promoter includes 3 CAT boxes, 1 SP1 and 1 E box. However, there was no consensus sequence for a TATA box in the 5'-flanking region. Putative regulatory sites of further upstream in the sequence revealed 6 LMO(2)COM, 5 NFAT, 2 LPOLYA-B, 3 GATA1, 2 AP4, 10 MZF1, 1 ETS1-B, 1 GATA3, 1 NKX25, 2 RORA1, 1 LYF1, 2 Ikaros2, 2 TCF11, 1 GATA-C and 1 FREAC7. Therefore, the 5'-flanking region of human pax-5 exon 1B could be involved in regulating the expression of human pax-5 and B-cell differentiation and development.
5' Flanking Region
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genetics
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Amino Acid Sequence
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Base Sequence
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Binding Sites
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genetics
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DNA
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chemistry
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genetics
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DNA-Binding Proteins
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genetics
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Exons
;
genetics
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Humans
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Molecular Sequence Data
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PAX5 Transcription Factor
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Sequence Analysis, DNA
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Transcription Factors
;
genetics
5.Expression of the transcription factor PAX5 in childhood acute leukemic cells.
Bei ZHANG ; Li-Jun TIE ; Qi-Dong YE ; Long-Jun GU ; Jing-Yan TANG ; Xiang-Liang YUAN ; Li-Song SHEN
Journal of Experimental Hematology 2006;14(1):6-10
To investigate transcription factor PAX5 expression characteristics in childhood acute leukemic cells, expression levels of PAX5 and CD19 mRNA in 6 hematological tumor cell lines and bone marrow cells of 6 normal children, 58 de novo patients and 4 relapse acute leukemic children, including 39 cases of B-ALL, 10 cases of T-ALL and 13 cases of AML, were detected by a real-time RT-PCR. The results showed that PAX5 and CD19 mRNA expression levels were 2.35% and 2.52% in Namalwa (B-cell lines) respectively, but almost not detectable in other T- and myeloid cell lines. Among clinical samples, expression of PAX5 mRNA in B-ALL was significantly higher than that in T-ALL and AML (P = 0.029 and P = 0.013 respectively). PAX5 expression was significantly lower in T-ALL and AML than that in normal controls. The difference of PAX5 mRNA expression levels between T-ALL and AML was not significant. Individual difference of PAX5 mRNA expression levels in children with B-ALL was great. Moreover, PAX5 mRNA expressions in de novo and relapse patients with B-ALL were significantly higher than those in remission (P = 0.011 and P = 0.006 respectively). As binding sites for B-cell specific activator protein have been identified in the promoter regions of CD19, the study found that in B-ALL, there was clear correlation between the expression levels of PAX5 and CD19, which was also studied by real-time RT-PCR. It is concluded that PAX5 transcripts are readily detectable and quantifiable in clinical materials with B-ALL by real-time RT-PCR. The strong PAX5 mRNA expression in some B-ALL can be considered to be particularly interesting for further analysis.
Adolescent
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Antigens, CD19
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biosynthesis
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genetics
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Cell Line, Tumor
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Child
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Child, Preschool
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Female
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Humans
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Infant
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Male
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PAX5 Transcription Factor
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biosynthesis
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genetics
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
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metabolism
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pathology
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RNA, Messenger
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biosynthesis
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genetics
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Transcription Factors
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biosynthesis
;
genetics
6.Deletions and rearrangements of PAX5 gene in B-lineage acute lymphoblastic leukemia.
Ji-fu ZHENG ; Sha-sha DONG ; Qian WANG ; Jin-lan PAN ; Su-ning CHEN ; Hui-ying QIU
Chinese Journal of Medical Genetics 2013;30(5):549-552
<b>OBJECTIVEb>To determine the frequency paired-box domain 5 (PAX5) gene alterations in B-lineage acute lymphoblastic leukemia (B-ALL) harboring 9p abnormalities and its implication for clinical prognosis.
<b>METHODSb>Bacterial artificial chromosomes RP11-344B23 and RP11-652D9 encompassing the PAX5 gene were selected. DNA was extracted with conventional method and labeled with fluorescein by nicking transition. Fluorescence in situ hybridization (FISH) was used to determine the rearrangement or deletion of the PAX5 gene in B-ALL harboring chromosome 9p abnormalities. Clinical and laboratory features of patients were analyzed.
<b>RESULTSb>Fifty cases were analyzed with FISH. Complete deletion was observed in 23 patients (46%), partial deletion was observed in 2 patients (4%), and rearrangement was detected only in 1 case. The total frequency of abnormalities was 52% (26/50). No significant difference was found in clinical features of patients with or without PAX5 rearrangement or deletion.
<b>CONCLUSIONb>The frequency of PAX5 gene alterations in B-ALL harboring 9p abnormalities was 52%. However, no significant difference was found between patients with and without PAX5 alterations.
Acute Disease ; Adolescent ; Adult ; Child ; Chromosomes, Human, Pair 9 ; genetics ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, B-Cell ; genetics ; Male ; Middle Aged ; PAX5 Transcription Factor ; genetics ; Sequence Deletion ; Young Adult
8.B/T-cell biphenotypic lymphoblastic lymphoma/leukemia: report of a case.
Ding-bao CHEN ; Ying WANG ; Lin DAI
Chinese Journal of Pathology 2013;42(10):704-705
Adult
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Biopsy
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CD3 Complex
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metabolism
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DNA Nucleotidylexotransferase
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metabolism
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Female
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Humans
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Leukemia, Biphenotypic, Acute
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metabolism
;
pathology
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Lymph Nodes
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metabolism
;
pathology
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Neck
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PAX5 Transcription Factor
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metabolism
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
metabolism
;
pathology
9.Significance of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia without reproducible chromosomal abnormalities.
Xiao-Ming LIU ; Li ZHANG ; Min RUAN ; Tian-Feng LIU ; Jia-Yuan ZHANG ; Fang LIU ; Ben-Quan QI ; Xiao-Juan CHEN ; Shu-Chun WANG ; Wen-Yu YANG ; Ye GUO ; Yao ZOU ; Yu-Mei CHEN ; Xiao-Fan ZHU
Chinese Journal of Contemporary Pediatrics 2016;18(4):287-291
<b>OBJECTIVEb>To identify the incidence of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnormalities and to investigate the association between PAX5 abnormalities and prognosis of ALL.
<b>METHODSb>Multiplex ligation-dependent probe amplification was used to determine the copy numbers of PAX5 gene in children newly diagnosed with B-ALL without reproducible chromosomal abnormalities between April 2008 and April 2013 and controls (children with non-hematologic diseases or tumors). The patients were classifiied into deletion group and non-deletion group based on the presence of PAX5 deletion.
<b>RESULTSb>Eighteen (21%) out of 86 children with B-ALL had PAX5 deletion. The deletion group had a significantly higher total white blood cell count at diagnosis than the non-deletion group (P=0.001). The Kaplan-Meier analysis demonstrated that the deletion group had a significantly lower disease-free survival (DFS) rate than the non-deletion group (0.69±0.12 vs 0.90±0.04; P=0.017), but there was no significant difference in the overall survival rate between the two groups (P=0.128). The Cox analysis showed that PAX5 deletion was a risk factor for DFS (P=0.03).
<b>CONCLUSIONSb>PAX5 deletion is an independent risk factor for DFS in B-ALL children without reproducible chromosomal abnormalities.
Acute Disease ; Adolescent ; Cell Lineage ; Child ; Child, Preschool ; Chromosome Aberrations ; Disease-Free Survival ; Female ; Gene Deletion ; Humans ; Infant ; Male ; PAX5 Transcription Factor ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; mortality
10.Effect of pax5 gene blocked by RNAi on biological characteristics of B cell malignant lymphoma.
Xiang-Liang YUAN ; Bei ZHANG ; Li-Min JIANG ; Li-Song SHEN
Journal of Experimental Hematology 2008;16(4):799-803
This study was aimed to investigate the biological characteristics of B hematological tumor cells such as proliferation, immunological phenotype and apoptosis by silencing pax5. The specific pax5 small hairpin RNA (shRNA) was synthesized by in vitro transcription. For evaluating the inhibition efficiency, the expression change at mRNA and protein levels were assessed by real-time RT-PCR and Western blot respectively. To detect the biological characteristics of pax5-silenced hematological tumor cells, the immunological phenotype, apoptosis and cell proliferation were measured by using real-time RT-PCR, MTT assay and flow cytometry respectively. The results showed that two shRNA were synthesized, both of which were effective to block pax5 expression. After being blocked by RNAi the immunological phenotype of pax5-silenced lymphoma cells was changed, the expressions of CD19 mRNA and protein were reduced, but the expression of IgM was not changed. As compared with control group, the effect on proliferation and apoptosis of lymphoma cells not could be detected after pax5 silencing. It is concluded that the pax5 plays important role in late differentiation of B cells, and may participate in signal transduction of lymphoma cells, but the effect on proliferation and apoptosis of lymphoma cells were not detected after RNAi, which need to be elucidated further.
Apoptosis
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genetics
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Gene Silencing
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Humans
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Lymphoma, B-Cell
;
genetics
;
metabolism
;
pathology
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PAX5 Transcription Factor
;
genetics
;
metabolism
;
RNA Interference
;
RNA, Messenger
;
genetics
;
metabolism
;
RNA, Small Interfering
;
genetics
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Tumor Cells, Cultured