Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Relationship between IKZF3 Gene Single Nucleotide Polymorphisms and Childhood Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between single nucleotide polymorphisms (SNPs) of IKAROS family Zinc finger 3 (IKZF3) gene and the risk of acute lymphoblastic leukemia (ALL) in children.@*METHODS@#The peripheral blood samples from 286 children with ALL and 382 healthy children were collected and divided into ALL group and control group, respectively. The genotypes of IKZF3 gene at rs62066988 C > T and rs12946510 C > T were detected by quantitative PCR with TaqMan detection system, and their correlation with ALL was analyzed.@*RESULTS@#The distribution frequencies of CC, CT and TT genotypes at rs62066988 in ALL group were 58.39%, 37.06% and 4.55%, respectively, while those in control group were 69.19%, 27.68% and 3.13%, respectively. The distribution frequencies of CC, CT and TT genotypes at rs12946510 in ALL group were 58.16%, 34.75% and 7.09%, respectively, while those in control group were 55.76%, 37.43% and 6.81%, respectively. Compared with the control group, the distribution frequency of CT/TT genotype at rs62066988 was significantly increased in the ALL group (OR=1.59, 95%CI: 1.16-2.19, P=0.004). However, there was no significant difference in the distribution of rs12946510 C > T polymorphism between ALL group and control group.@*CONCLUSION@#The CT/TT genotype of IKZF3 at the site of rs62066988 is associated with the increased risk of ALL in children.

Effect of increasing the intensity of chemotherapy on the prognosis of acute lymphoblastic leukemia in children with IKZF1 deletion / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of acute lymphoblastic leukemia (ALL) in children with IKAROS family zinc finger 1 (IKZF1) deletion, and to observe the effect of increasing the intensity of chemotherapy on the prognosis of this disease.@*METHODS@#A total of 278 children diagnosed with ALL between December 2015 and February 2018 were systematically treated according to the Chinese Children's Leukemia Group-ALL 2008 protocol (CCLG-ALL 2008). The patients were divided into an IKZF1-deleted group and a control group according to the presence or absence of IKZF1. The IKZF1-deleted group was treated with the regimen for high-risk group (HR) in the CCLG-ALL 2008 protocol, while the control group received different intensities of chemotherapy according to clinical risk classification. The clinical features and event-free survival rate (EFS) were compared between the two groups.@*RESULTS@#A total of 24 (8.6%) cases of 278 children were found to have large deletions of exons of the IKZF1 gene. The IKZF1-deleted group had significantly higher proportions of cases with white blood cell count ≥50×10/L at initial diagnosis, BCR-ABL1 fusion gene positive, minimal residual disease ≥10% on the 15th day of induction remission treatment, minimal residual disease-high risk and clinical risk classification-high risk compared with the control group (P<0.05). The 3-year EFS rate (76%±10%) in the IKZF1-deleted group was lower than that in the control group (84%±4%), but with no significant difference between the two groups (P=0.282). The estimated 3-year EFS rate in the IKZF1-deleted-non-HR group (actually treated with the chemotherapy regimen for HR in the CCLG-ALL 2008 protocol) was 82%±12%, which was lower than that in the control-non-HR group (86%±5%), but there was no significant difference (P=0.436).@*CONCLUSIONS@#ALL children with IKZF1 deletion have worse early treatment response, and increasing the intensity of chemotherapy might improve the prognosis.

Expression of Ikaros and FUT4 in Children's Acute Lymphoblastic Leukemia and Their Relationship / 中国实验血液学杂志

OBJECTIVE@#To explore the possible molecular mechanism of Ikaros regulation on FUT4 expression by analyzing the correlation of the functional state of Ikaros with level of FUT4 expression, so as to provide the theoretical basis for personalized treatment in children with ALL.@*METHODS@#The subtypes of Ikaros were identified by nested PCR and sequencing. The expression level of FUT4 was detected by quantitative PCR and analyzed by ΔΔCt method in the early stage of treatment, remission and relapse of ALL.@*RESULTS@#Ik1 and Ik2 were the main functional subtypes, and the dominant negative Ikaros was Ik6; the Ik6 was detected in 23 patients with ALL. It was found that 2.73% patients expressing Ik6 alone and 18.18% patients with heterozygous expression were detected. The expression of FUT4 in the newly diagnosed ALL was higher than that in the control group, and the functional Ikaros negatively correlated with the FUT4 expression(r=-0.6329).@*CONCLUSION@#Dominant negative Ikaros closely correlated with the relapse of acute lymphoblastic leukemia in children. The functional Ikaros negatively correlated with FUT4 expression. Ikaros inhibit the transcriptional activity of FUT4, that may be the molecular mechanism of Ikaros regulating the expression of FUT4.

Effects of minimal residual disease level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of minimal residual disease (MRD) level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia (B-ALL).</p><p><b>METHODS</b>A total of 152 children with newly-diagnosed B-ALL who had complete remission after the first cycle of the chemotherapy and had complete follow-up information were enrolled in this study. According to the MRD detection by flow cytometry on day 33 of remission induction, they were divided into three groups: standard-risk (SR) group (MRD <10; n=60), intermediate-risk (IR) group (10≤ MRD <10; n=55), and high-risk (HR) group (MRD ≥10; n=37). Nested RT-PCR was used to determine the IKZF1 genotype of all children before chemotherapy. The effects of MRD level on day 33 of remission induction and IKZF1 genotype on the recurrence-free survival (RFS) of children with B-ALL were analyzed.</p><p><b>RESULTS</b>There were 7 common IKZF1 subtypes in all the 152 children with B-ALL: IK1, IK2/3, IK4, IK6, IK8, IK9, and IK10. Of the 152 children, 130 had functional subtypes of IKZF1 and 22 had non-functional subtypes of IKZF1. During the follow-up period, relapse occurred in 26 (17%) children, and the recurrence rate was highest in the HR group (P<0.05). However, there was no significant difference in the recurrence rate between the SR group and the IR group (P>0.05). The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1 (P<0.01). The predicted 5-year RFS rates in the SR, IR, and HR groups were (94.2±2.9)%, (86.7±3.8)%, and (56.2±4.5)% respectively (P<0.05). The 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 (P<0.01). There was no significant difference in the predicted 5-year RFS rate between the children with functional subtypes of IKZF1 and those with non-functional subtypes of IKZF1 in the SR group (P>0.05). However, the predicted 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 in the IR group and the HR group (P<0.05).</p><p><b>CONCLUSIONS</b>B-ALL children with non-functional subtypes of IKZF1 have a high recurrence rate, and the recurrence rate will be even higher in B-ALL children with non-functional subtypes of IKZF1 and MRD ≥10 on day 33 of chemotherapy.</p>

Análise genômica de deleções completas de IKZF1 em leucemias linfoblásticas agudas pediátricas / [Genomic analysis of complete IKZF1 deletions in pediatric acute lymphoblastic leukemias]

Introdução: A leucemia de células precursoras B (LLA-CPB) pediátrica é caracterizada por alterações citogenético-moleculares recorrentes, cuja identificação é essencial para aestratificação de risco terapêutico e adequação do tratamento ao risco de recaída em cada paciente. Recentemente estudos genômicos identificaram que deleções em IKZF1 (ΔIKZF1)podem ser preditivas de maior risco de recaída. As ΔIKZF1 foram rastreadas inicialmente por amplificação multiplex dependente de ligação de sondas (MLPA), no entanto, ametodologia é pouco sensível para a avaliação de doença residual mínima. Para tanto, estudos recentes desenvolveram técnicas de PCR multiplex (MP-PCR). Como as MP-PCRnão detectam IKZF1 Δ1-8 (~30% das LLA-CPB pediátricas), este trabalho teve como objetivo investigar as características das IKZF1 Δ1-8 nas LLA-CPB pediátricas. Metodologia: Os sujeitos desta pesquisa foram crianças e adolescentes (< 18 anos) comLLA-CPB e IKZF1 Δ1-8. Inicialmente uma coorte de descoberta (n = 6) foi caracterizada por microarranjo. Em seguida, alterações de número de cópias (CNAs) no cromossomo 7 foramavaliadas na coorte de investigação (n = 45) através de MLPA customizado. A partir dos dados de CNA, os pontos de quebra das deleções foram sequenciados por PCR multiplexou PCR invertida de longa distância. Com as sequências de ponto de quebra, investigamos sequências sinais de recombinação de RAG (RSSs), além de motivos CpG, estrutura secundária do DNA nas regiões de quebra e dados públicos do ENCODE de DNase eChIP-seq. Características demográficas e CNAs de amostras com IKZF1 Δ1-8 e demais deleções foram comparadas no programa SPSS 18, enquanto diferenças na distribuição de motivos nas regiões de quebra foram avaliados no GraphPad Prism 5. Valores p < 0,05 foram interpretados como estatisticamente significantes...

Background: Childhood B-cell precursor acute leukemia is characterized by recurrent cytogenetic and molecular alterations. Their identification is crucial for both risk stratificationand treatment management of patients. Recently, genomic studies have identified IKZF1 deletions (ΔIKZF1) as a valuable predictor of relapse. ΔIKZF1 have been screened by multiplex probe amplification assay (MLPA) in various studies, although the methodologylacks sensitivity for minimal residual disease evaluation. Therefore, novel studies have developed multiplex PCR (MP-PCR) tests with greater sensitivity. Since MP-PCR is still unable to identify IKZF1 Δ1-8 (~30% of recurrent deletions of BCP-ALL), this study aimed to investigate the main characteristics of childhood BCP-ALL cases with IKZF1 Δ1-8. Methods: This study enrolled children aged <18 years diagnosed with BCP-ALL and IKZF1 Δ1-8. First,a discovery cohort (n = 6) was analyzed with CytoScan HD array. Thereafter, CNAs within chromosome 7 were alalyzed in a validation cohort (n = 45) using an in-house MLPA. Thebreakpoints were sequenced after multiplex (MP-PCR) and long-distance inverse PCR (LDIPCR). After all, the possible mechanisms underlying occurrence of deletions were alsoinvestigated using a nucleotide-based similarity approach, along with DNase and ChIP-seq data retrieved from ENCODE database. Statistical analysis of demographic characteristics were compared with SPSS 18, while sequence motifs analyzed on GraphPad Prismsoftware...

Significance of ikaros family zinc finger 1 deletion in pediatric B-acute lymphoblastic leukemia without reproducible cytogenetic abnormalities / 中华儿科杂志

<p><b>OBJECTIVE</b>To identify ikaros family zinc finger1 (IKZF1) deletion in patients with pediatric B cells-acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnomalities and further investigate its value in this part of patients' pathogenesis and prognosis.</p><p><b>METHOD</b>The study was approved by the institutional review board of the authors' hospital and informed consent was obtained from the patients and/or their legal guardians. Data of 96 children with B-ALL patients without reproducible cytogenetic abnormalities whose bone marrows specimens were enough for DNA extraction for the detection were retrospectively selected. All the patients were diagnosed and systematically treated according to CCLG-ALL2008 in our hospital from April 2008 to April 2013. The 96 patients were divided into two groups according to the result of IKZF1's detection by multiplex ligation-dependent probe amplification (MLPA): The cases that with any of eight exons of IKZF1 deleted were entered into"Group with IKZF1 deletion"otherwise entered"Group without IKZF1 deletion". Disease free survival (DFS), event-free survival (EFS) and overall survival (OS) were compared between the two groups.</p><p><b>RESULT</b>Nineteen out of 96 B-ALL patients without reproducible cytogenetic abnormalities had IKZF1 deletion (20%). Three of 19 patients with IKZF1 deletions of the whole gene; ten of 19 patients with IKZF1 deletions of exon 1; 4 of 19 patients with IKZF1 deletions of exons 4-7; one of 19 patients with IKZF1 deletions of exons 2-7 and one of 19 patients with IKZF1 deletions of exons 1-6. Whose white blood cell (WBC) ≥ 50 × 10(9)/L inIKZF1 diletion group was more than whthout IKZF1 deletion group(42% vs. 13%, P=0.004). Patients with IKZF1 deletions had a lower 3-year DFS (0.67 ± 0.13 vs. 0.93 ± 0.04, P=0.001); EFS (0.67 ± 0.13 vs. 0.90 ± 0.04, P = 0.012) and OS(0.79 ± 0.09 vs. 0.96 ± 0.02, P=0.010) compared to those without IKZF1 deletions. Excluding the influence of sex, age, WBC count at diagnosis, cerebrospinal fluid state and prednisone response IKZF1 deletion still affected the patients' DFS, EFS and OS ( P<0.05 for all comparisons).</p><p><b>CONCLUSION</b>Some of pediatric B-cell precursor ALL without reproducible cytogenetic abnormalities had been detected to have IKZF1 deletion; IKZF1 deletion is an independent poor prognostic factor in these patients.</p>

Significance of IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To identify IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia (B-ALL) in children, and to investigate the association between such abnormalities and prognosis.</p><p><b>METHODS</b>Multiplex ligation-dependent probe amplification (MLPA) was applied to detect IKZF1 gene copy number abnormalities in 180 children diagnosed with BCR/ABL-negative B-ALL. These children were classified into IKZF1 deletion group and IKZF1 normal group according to the presence or absence of IKZF1 gene deletion. The association between IKZF1 copy number abnormalities and prognosis of children with BCR/ABL-negative B-ALL was analyzed retrospectively.</p><p><b>RESULTS</b>Among 180 children, 27 (15.0%) had IKZF1 deletion; among the 27 children, 4 had complete deletions of 8 exons of IKZF1 gene, 17 had deletion of exon 1, 3 had deletions of exons 4-7, and 3 children had deletions of exons 2-7. Compared with those in the IKZF1 normal group, children in the IKZF1 deletion group had higher white blood cell (WBC) count and percentage of individuals with high risk of minimal residual disease at the first visit. IKZF1 deletions often occurred in BCR/ABL-negative children with no special fusion gene abnormalities. They were frequently accompanied by abnormalities in chromosomes 11, 8, 5, 7, and 21. The analysis with Kaplan-Meier method showed that disease-free survival (DFS) in the IKZF1 deletion group was significantly lower than that in the IKZF1 normal group (0.740 ± 0.096 vs 0.905 ± 0.034; P=0.002). Cox analysis showed that after exclusion of sex, age, initial WBC count, cerebrospinal fluid state at the first visit, prednisone response, and chromosome karyotype, IKZF1 deletion still affected the children's DFS (P<0.05).</p><p><b>CONCLUSIONS</b>Some children with BCR/ABL-negative B-ALL have IKZF1 deletion, and IKZF1 deletion is an independent risk factor for DFS in children with BCR/ABL-negative B-ALL.</p>

Correlation of IKZF1 Gene with Malignant Tumors and Systemic Lupus Erythematosus / 中国实验血液学杂志

IKZF1 gene located in 7p12 of chromosome, and Ikaros family zinc finger encoded by IKZF1, are lymphoid-restricted transcription factors. In recent years, it has been demonstrated that the mutation of IKZF1 gene involved in proliferation, metastasis and prognosis of many malignant tumor except acute lymphoblastic leukemia, and also involved in complex phenotypes and susceptibility to systemic lupus erythematosus. This review briefly introduces the molecular structure and physiological function of Ikaros, focusing on its function and molecular mechanism in proliferation, metastasis and prognosis of malignant tumors, and its role in the systemic lupus erythematosus.

Effect of Ikaros in B Cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

The Ikaros - a DNA-binding zinc finger protein, acting as a regulator of chromatin remodeling and gene transcription, is crucial for regulating the development and function of the immune system and acting as a master regulator of hematopoietic differentiation. Function-loss mutations of IKZF1, gene encoding Ikaros are frequent in B cell acute lymphoblastic leukemia (B-ALL) and are associated with a poor prognosis. This review briefly summarizes the available data regarding the structure and function of Ikaros, the role of Ikaros as a tumor suppressor in B-ALL, and its regulation mechanism.

Construction of IK6 recombinant lentiviral vector and its expression and biologic feature in THP1 cells / 中国实验血液学杂志

The purpose of this study was to construct a lentiviral vector carrying IK6 gene and to observe the expression of IK6 as well as related biologic feature in THP1 cells, so as to provide an effective method to further investigate the role of this gene in leukemia. The IK6 gene was obtained by using reverse transcription polymerase chain reaction (RT-PCR). Then IK6 was recombined with the pGC-FU vector to construct a recombinant lentiviral vector named pGC-FU-IK6 gene-GFP,which was confirmed by PCR and sequencing. The 293T cells were transfected with pGC-FU- IK6-GFP by using Lipofectamine 2000. After examining the titer of the virus, pGC-FU- IK6-GFP was used to transfect THP1 cells. The transfection efficiency was detected by flow cytometry, and the expression level of mRNA and IK6-GFP fusion protein were confirmed by RT-PCR and Western blot respectively. Then the impact of IK6 on apoptosis and cell cycle was analyzed. The results showed that the IK6 gene was obtained by RT-PCR and connected into the linearized lentiviral vector to successfully constructed target plasmid named pGC-FU-IK6-GFP with Amp resistant. The target plasmid was transfected into 293T cells and the virus titer was 2.0×10(9)TU/ml. Next, THP1 cells were transfected with pGC-FU-IK6-GFP and the efficiency was up to 90%. The detection of the IK6 mRNA and IK6-GFP fusion protein in target cells showed that IK6 could promote target cell clone formation and inhibit apoptosis, but had no significant effect on the cell cycle. It is concluded that virus vector carrying IK6 gene had been successfully constructed and expressed in THP1 stably. Biology studies of target THP1 cell shows that the IK6 is likely to interfere with the function of normal Ikaros protein as tumor suppressor, and it exerts a potential anti-apoptotic effect. Thus, IK6 can promote leukemia cell growth. However, there is no significant effect on the cell cycle. It provides an effective method for exploring the function of IK6 in acute myeloid leukemia.

C2H2 zinc-finger recognition of biomolecules / 药学学报

C2H2 zinc-finger motif presents in 3% of proteins that are encoded in the human genome, and has the abilities to recognize DNA, RNA and protein. With nearly 3 decades of efforts, the mechanisms of zinc-finger mediated biomolecule recognitions have been studied to various extents. Zinc-finger binds into the major groove of DNA double helix, establishes an one-to-one recognition format between DNA bases and certain amino acids in a zinc-finger, and achieves specificity based on DNA sequences. While RNA molecules show a large variety in their structures, zinc-finger recognizes RNA through the collected information of specially displayed bases and special backbone folding. Initial studies have been performed on zinc-finger mediated protein-protein interactions. Existing data indicate multiple recognition modes. The studies on molecular mechanism have supported the development of engineered zinc-fingers, which have been introduced into applications. For its wide existence, large functional diversity and potential in translational applications, zinc-finger deserves a systematic study in every aspect.

The abnormal expression of IKZF1 encoded protein-IKAROS in B-ALL children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the isoforms of IKAROS in the bone marrow samples from children with acute B-lineage lymphoblastic leukemia (B-ALL) and to investigate the relationship between frequency of dominant-negative (DN) IKAROS isoforms and prognosis of B-ALL, and to preliminarily study the relevant mechanism.</p><p><b>METHODS</b>A total of 137 children with newly diagnosed B-ALL, who sequentially entered the Department of Hematology and Oncology, Shanghai Children's Medical Center between January 2005 and September 2010, were included in the study. Nest-PCR, Sanger sequencing, and TA cloning were used to analyze the expression of IKAROS isoforms in these children. The relationship between frequency of DN IKAROS isoforms and prognosis of B-ALL was investigated.</p><p><b>RESULTS</b>Of the 137 children with newly diagnosed B-ALL, 16 had expression of IK6, 14 had expression of IK4, and 2 had expression of IK7. There was significant difference in 2.5-year event-free survival between the cohorts of DN IKAROS and non-DN IKAROS (P=0.01). Analysis of the 10 paired of diagnosis/relapse samples from 10 patients with recurrence showed that 8 of 10 paired diagnosis and relapse samples had inconsistent expression of IKAROS isoforms. The rate of IK6 expression in relapse samples from 21 relapse ALL patients was significantly higher than in the 137 children with newly diagnosed ALL (62% vs 12%, P<0.01).</p><p><b>CONCLUSIONS</b>Expression of DN IKAROS isoforms can be a poor prognostic factor in B-ALL and is closely associated with recurrence of B-ALL.</p>

Expression and clinical significance of IKZF1 gene IK6 isoform in adult acute lymphoblastic leukemia / 中国实验血液学杂志

This study was aimed to detect the expression of IKZF1 gene isoforms in bone marrow cells of patients with adult acute lymphoblastic leukemia and to investigate the clinical characteristics and prognosis of patients with IK6 isoform. The expression of IKZF1 gene isoforms were measured by nested RT-PCR in 79 newly diagnosed ALL patients. The clinical characteristics of IK6 positive patients and overall survival, disease-free survival of the IK6 positive group and IK6 negative group were compared. The results showed that IK1 and IK2/3 were the functional isoform while the IK4, IK6, IK8 and IK9 were the dominant negative isoform in adult ALL. The dominant negative isoform IK6 accounted for 34.4% in B-ALL patients and accounted for 22.2% in T-ALL patients. The BCR/ABL1 positive rate and the percentage of high risk patients in IK6 positive group was higher than that of IK6 negtive group in B-ALL patients (P = 0.027, P = 0.048). The expression of IK6 isoform did not correlate with sex, age and WBC count of B-ALL and T-ALL patients. The overall survival and disease-free survival of IK6 positive group were both lower than that of IK6 negtive group in Ph negative B-ALL patients (P = 0.009, P = 0.002). It is concluded that IK6 is a main isoform of the expression of IKZF1 gene in adult ALL patients, and can be used as a prognostic factor for guiding treatment in Ph negative B-ALL patients.

Expression characteristics of isoforms of Ikaros and Helios in patients with leukemia and their mechanism / 中国实验血液学杂志

This study was aimed to investigate the expression characteristics of two transcriptional factors in Ikaros family, Ikaros and Helios isoforms and their mechanism, as well as their correlation with clinical parameters, which play important roles in transcriptional regulation of hematopoiesis. Expression of Ikaros and Helios isoforms in a total of 163 patients with leukemia and correlations between Ikaros and Helios isoforms were analyzed by PCR. The results showed that different expression patters of Ikaros and Helios isoforms existed in leukemia patients, that is, Ikaros isoform (Ik-6) was predominantly expressed in acute lymphoblastic leukemia (ALL) with BCR/ABL fusion gene, while Helios isoform (He-i) was overexpressed in T-cell ALL patients. The results of cloning and sequencing demonstrated that the isoforms of Ikaros and Helios had different genetic alterations. The statistical correlation between these two isoforms not was found in this study, although interaction between Ikaros and Helios has been reported. It is concluded that although Ikaros and Helios belong to the same family with similar structure of zinc fingers, their isoforms have different expression profile, specific genetic alterations, and different clinical relevance in patients with leukemia. The connection and interaction between Ik-6 and He-i needs further research.

Analysis of IKAROS6 expression in 73 patients with chronic myelogenous leukemia / 中国实验血液学杂志

This study was aimed to evaluate IKAROS6 expression in patients with chronic myelogenous leukemia (CML) and its clinical significance. cDNAs from 73 CML patients were amplified by PCR and sequenced for IKAROS expression to elucidate clinical characteristics in IKAROS6 positive patients. The results showed that there was no IKAROS6 gene expression in 8 healthy controls and 15 CML patients in chronic phase and accelerated phase, and 15 cases (35.71%) were IKAROS6 positive in lymphoblast crisis samples among 42 newly diagnosed CML; however, none was found in myeloblast crisis of 16 newly diagnosed CML. Among 42 lymphoblast crisis of CML, the complete remission (CR) rate of IKAROS6 expression positive patients reached 40% (6/15), which was obviously lower than that in IKAROS6 negative patients (85.19%, 23/27) (p < 0.01), IKAROS6 positive patients relapsed after CR for 15 (2 - 18) months with relapse rate 66.7% (4/6), which was higher than that in expressed wild type IKAROS gene patients (21.74%, 5/23) (p < 0.05). It is concluded that abnormal expression of IKAROS gene dominated by IKAROS6 isoforms can be detected in lymphoblast crisis samples of CML patients. Abnormal expression of IKAROS gene may be an important factor in lymphoblast crisis of CML. Therefore, detection of IKAROS gene expression may be important for target therapy and evaluation of clinical prognosis of CML patients.

Comparative proteomics research of apoptosis initiation induced by homoharringtonine in HL-60 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the related proteins of apoptosis initiation induced by homoharringtonine (HHT) in HL-60 cells.</p><p><b>METHODS</b>After establishment of an apoptosis initiation model induced by HHT in HL-60 cells, proteins of untreated and HHT treated HL-60 cells were extracted, and the two-dimensional polyacrylamide gel electrophoresis (2-DE) maps of the extracted proteins were established by using the immobilized pH gradient (IPG) two-dimensional electrophoresis respectively. The alteration protein spots were identified with assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database searching.</p><p><b>RESULTS</b>Proteomics analysis showed that proteins including MHC class I antigen, calbindin D-28K, chloride channel protein 6, oncoprotein 18, zinc finger protein Helios and apoptosis inhibitor like protein 2 were involved in apoptosis initiation induced by HHT.</p><p><b>CONCLUSION</b>The present study might conduce to the researches of HL-60 cells carcinogenesis and pave the way to exploit drug precursor related to HHT and initiation of apoptosis in HL-60 cells.</p>