RPL5 Is a Candidate Tumor Suppressor on 1p22.1 in Multiple Myeloma of Which the Expression Is Linked to Bortezomib Response

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2969-2969
Author(s):  
Isabel JF Hofman ◽  
Mark van Duin ◽  
George Mulligan ◽  
Ellen Geerdens ◽  
Emanuela Garelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Suppressor ◽  
Mrna Expression ◽  
Integration Site ◽  
Lymphoblastic Leukemia ◽  
Expression Level ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Expression Levels

Abstract Chromosomal region 1p22 is deleted in ~20% of multiple myeloma patients, suggesting the presence of an unidentified tumor suppressor gene in this region. Using high resolution copy number arrays, we delimit a 58 kb minimal deleted region on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Although mutations in 1p22 genes are rare in multiple myeloma, the tumor suppressor role of EVI5 and RPL5 may be supported by the fact that these genes show the highest frequency of mutations predicted to impair protein function on 1p22. Interestingly, inactivation of RPL5 was also recently described in T-cell acute lymphoblastic leukemia (T-ALL) and glioblastoma. We found that 1p22 deleted patients have significantly lower levels of EVI5 and RPL5 mRNA expression (59% and 71% residual expression respectively; p<0.0001 for each gene). Whereas 1p22 deletion status correlates well with EVI5 expression in all patients, it is a bad predictor of RPL5 expression level in some cases, suggesting that other mechanisms besides 1p22 deletion can downregulate RPL5 expression in multiple myeloma. Deletion of 1p22 has been associated with decreased progression free (PFS) and overall survival (OS) in newly diagnosed multiple myeloma (Hebraud et al., Leukemia, 2013). We saw that low mRNA expression of EVI5 and RPL5 also correlates with worse survival in diagnosis but not in relapse cases. Interestingly, RPL5 but not EVI5 mRNA expression levels were significantly lower in multiple myeloma patients responding to bortezomib compared to patients that are not responding (68% residual RPL5 expression in responders versus non-responders). The clinical relevance of these findings is illustrated by the observation that PFS of newly diagnosed patients with low RPL5 expression was significantly longer when they were treated on a bortezomib containing protocol (median PFS bortezomib protocol 29.8 months versus 18.7 months for non-bortezomib, p=0.03, data phase III HOVON-65/ GMMG-HD4 trial). In contrast, PFS of RPL5 high patients was not influenced by bortezomib. These associations between RPL5 expression level and bortezomib response were confirmed when performing the same analyses on the PFS data from relapse patients in the APEX trial. For low EVI5 expressing patients, there was a non-significant trend towards benefit from bortezomib which was not present in the EVI5 high cases. Taken together, these data suggest that RPL5 expression levels are a better biomarker for bortezomib response than 1p22 deletion. In conclusion, we provide genetic data that narrow down the list of candidate tumor suppressors on 1p22 to EVI5 and RPL5. Although the exact role of these genes in suppressing multiple myeloma disease progression remains to be determined, we identify low RPL5 expression levels in multiple myeloma as a novel, clinically relevant biomarker associated with initial response and survival benefit upon treatment with bortezomib. Disclosures Mulligan: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Delforge:Amgen: Honoraria; Novartis: Honoraria; Celgene Corporation: Honoraria; Janssen: Honoraria. Sonneveld:Janssen-Cilag, Celgene, Onyx, Karyopharm: Honoraria, Research Funding; novartis: Honoraria.

Wilms Tumor 1 Gene Mutations in Adult Acute T-Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2516-2516
Author(s):  
Sandra Heesch ◽  
Nicola Goekbuget ◽  
Jutta Ortiz Tanchez ◽  
Cornelia Schlee ◽  
Stefan Schwartz ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Wilms Tumor ◽  
Lymphoblastic Leukemia ◽  
Single Amino Acid ◽  
Newly Diagnosed ◽  
Expression Levels ◽  
Wilms Tumor 1 ◽  
Standard Risk ◽  
Wt1 Protein ◽  
Mrna Expression Levels

Abstract The wilms tumor 1 gene (WT1) encodes a transcriptional regulator involved in normal hematopoietic development. The role of WT1 in acute leukemia has been underscored by the finding of WT1 overexpression in subsets of patients (pts) associated with an increased relapse risk. In addition mutations of WT1 have been found in about 10–15% of acute myeloid leukemia (AML) pts and have recently shown to predict inferior survival. Thus far, larger studies have not yet determined the frequency and impact of WT1 mutations in acute T-lymphoblastic leukemia (T-ALL). Herein, we have analyzed WT1 mutations and WT1 mRNA expression levels in a large cohort of T-ALL including 239 newly diagnosed adult pts treated on the GMALL protocols 0699 and 0703. Diagnostic bone marrow specimens were studied for WT1 mutations by DNA sequencing. In addition, samples were immunophenotyped, and mRNA expression of the molecular markers HOX11, HOX11L2, ERG, BAALC, as well as WT1 were determined by real-time RT-PCR. Twenty (8%) of the 239 analyzed T-ALL pts had WT1 mutations (WT1mut) [20 pts had mutations in exon 7 (WT1mut7), with 2 pts having coexisting mutations in exon 9 (WT1mut9)]. WT1mut7 were frameshift or nonsense mutations predicted to result in a truncated WT1 protein, whereas WT1mut9 were missense mutations leading to single amino-acid substitutions. WT1mut and WT1 wildtype (WTwt) pts did not significantly differ with respect to clinical parameters at diagnosis (e. g. age, leukocyte count, and sex). WT1mut cases were characterized by immature features such as an early immunophenotype (45% of WT1mut showed an early T-ALL immunophenotype as compared to only 25% of WT1wt), and WT1mut also showed higher levels of CD34 expression as determined by flow cytometry (WT1mut median: 46% vs. WT1wt median: 2 %; P=0.03). Moreover, WT1mut had significantly higher WT1 mRNA expression levels [WT1mut median: 0.05 (range: 0–0.395) vs. WT1wt median: 0 (range: 0–0.15); P&lt;0.001]. Significant differences were not observed in the complete remission rate nor overall survival or relapse free-survival (RFS) between WT1mut and WT1wt pts. However, in the standard risk group of thymic T-ALL 80% (4/5) of WT1mut relapsed as compared to 28% (25/89) of WT1wt thymic pts [P=0.01; RFS at 18 months: 20% (SE: ±18) for thymic WT1mut vs. 82% (SE: ±4) for thymic WT1wt pts; P=0.008]. In conclusion, in adult T-ALL WT1 mutations are present in 8% of newly diagnosed pts and are located in the same region as reported in AML expected to impair the DNA binding ability of the WT1 protein. Similar to findings in AML, WT1mut cases are characterized by immature features pinpointing to a genetic hit in hematopoietic progenitors likely harboring bilineage potential. The prognostic implications of WT1 mutations in standard risk thymic T-ALL will have to be further validated in independent studies and may in future direct molecularly-based treatment stratification.

MicroRNA Profiling In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 302-302 ◽  
Author(s):  
Sophie Corthals ◽  
Su Ming Sun ◽  
Rowan Kuiper ◽  
Yvonne de Knegt ◽  
Annemiek Broyl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Suppressor ◽  
Mrna Expression ◽  
Board Of Directors ◽  
Mirna Expression ◽  
Plasma Cells ◽  
High Expression ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Mirna Clusters

Abstract Abstract 302 Background: Multiple Myeloma (MM) is a plasma cell malignancy, characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Prognostic factors in MM include translocations and ISS stage; still, the clinical course is difficult to predict. MicroRNAs (miRNAs) are a class of small non-coding single stranded RNAs involved in posttranscriptional gene regulation, which may be of use in defining MM prognosis and outcome. MiRNAs regulate protein levels by binding to either partially or complete complementary sites in messenger RNAs (mRNAs), leading to translational repression or transcript degradation respectively. In this manner, miRNAs play a role in critical biological processes including cellular growth and differentiation. Specific disease related miRNAs in both acute myeloid leukemia and chronic lymphocytic leukemia have been found with specific miRNA signatures associated with different cytogenetic subtypes. Until now, information available for miRNA expression in MM is limited. Methods: MiRNA expression profiling was performed in 45 newly diagnosed MM patients enrolled in the HOVON-65/GMMG-HD4 trial; a randomized, phase III trial performed to evaluate the efficacy of bortezomib prior to high-dose melphalan (HDM) for response, progression free survival (PFS) and overall survival (OS) in patients with newly diagnosed MM. As controls, four healthy BM samples were obtained from subjects undergoing BM harvest for allogeneic transplantation donorship. For all samples, BM derived CD138 selected plasma cells (PCs) with a minimum purity of > 80% were obtained. RNA was isolated using the miRVANA kit, with subsequent miRNA profiling by TaqMan Human MicroRNA Array v1.0. Unsupervised hierarchical clustering with the centered correlation metric with average linkage was performed using BRB-array tools 3.6.0. For survival analysis, miRNA expression was divided in quartiles: the top quartile vs the rest to identify cases with high expression and the bottom quartile vs the rest for cases with low expression. Log-rank tests for univariate association with PFS and OS were performed for each of the 365 miRNAs using the false discovery rate to correct for multiple testing. Chromosomal abnormalities t(4;14), t(11;14), t(14;16) and deletion 13q14 were determined by FISH analysis. MiRNA expression was compared to mRNA expression, available for 39 out of 45 MM patients, using a Spearman's rank correlation test. mRNA expression was determined by Affymetrix U133 Plus 2.0 arrays (Broyl et al., Blood 2010). Results: Clustering resulted in a dendrogram with 5 clear branches, consisting of 4 MM clusters and 1 normal BM cluster. The MM clusters are characterized by up- and downregulation of distinctive miRNAs: cluster A: upregulation of miRNA clusters miRNA-17∼92 and miRNA-106∼25 (n=23); cluster B: upregulation of miRNA-130a and miRNA-424 (n=8); cluster C: upregulation of miRNA-576 and miRNA-106b (n=9) and cluster D: upregulation of miRNA-372 and miRNA-200a (n=4). An additional cluster of one sample was not defined. MiRNAs predominantly expressed in normal BM were miRNA-28 and miRNA-30c. None of the miRNA clusters correlated with cytogenetic subgroups, i.e. deletion 13q14, t(4;14), t(11;14), and t(14;16) Still, a supervised approach showed significantly higher expression of miRNA-122a, miRNA-33, miRNA-489, miRNA-519e, and miRNA-555 in patients with t(11;14). Upregulation of let-7f, miRNA-194 and miRNA-296 expression were found to be associated with better OS with borderline significance (P = .06). Finally, a significant inverse correlation between miRNA-21 expression and gene expression of two of its validated targets, PDCD4 (P = 2× 10−4) and RECK (P = 8×10−4) was found. PDCD4 is a novel tumor suppressor, whose functions include inhibition of translation through eIF4A/eIF4G. RECK has been shown to be involved in angiogenesis, through inhibition of MMP2 and MMP9. Conclusion: miRNA expression in MM is deregulated compared to normal PCs and MM patients can be classified according to their miRNA expression pattern in four clusters. Furthermore, a trend was found for high expression of miRNAs let-7f, miRNA-194 and miRNA-296 with increased OS. Integration of miRNA and mRNA data shows the putative interaction between miRNA-21 and two of its validated targets; tumor suppressor gene PDCD4 and RECK, suggesting a functional relationship between miRNA expression and development of MM. Disclosures: Sonneveld: Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

scholarly journals The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

2020 ◽  
Vol 13 (12) ◽  
pp. 451
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Paola Deias ◽  
Francesca Patriarca
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Cellular Targets ◽  
Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

scholarly journals Expression Analysis of Circulating miR-22, miR-122, miR-217 and miR-367 as Promising Biomarkers of Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Fatemeh hosseinpour-soleimani ◽  
Gholamreza Khamisipour ◽  
Zahra Derakhshan ◽  
Bahram Ahmadi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Lymphoblastic Leukemia ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Quantitative Real Time Pcr ◽  
Expression Levels

Abstract Background Currently, the role of serum-based biomarkers such as microRNAs in cancer diagnosis has been extensively established. This study aimed to determine expression levels of bioinformatically selected miRNAs and whether they can be used as biomarkers or a new therapeutic target in patients with Acute Lymphoblastic Leukemia (ALL). Materials and Methods The expression levels of serum miR-22, miR-122, miR-217, and miR-367 in 21 ALL patients and 21 healthy controls were measured using quantitative real-time PCR. The receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) was used to assess candidate miRNAs' diagnostic value as a biomarker. Results The results showed that miR-217 was markedly decreased in patients with ALL compared to controls. Moreover, miR-22, miR-122, and miR-367 were found to be upregulated. Furthermore, ROC analysis showed that serum miR-217 and miR-367 could differentiate ALL patients from the healthy individuals, while miR-22 has approximate discriminatory power that requires further investigation. Conclusion Collectively, the results suggested that miR-217 may play a tumor suppressor role in ALL, whereas miR-22, miR-122, and miR-367 could function as an oncogene. Overall, miR-22, miR-217, and miR-367 could be considered possible biomarkers for the early diagnosis of ALL.

scholarly journals Three Drug Regimens for Newly Diagnosed Multiple Myeloma Transplant-Ineligible Elderly Patients - a Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5574-5574
Author(s):  
Abdul Aziz Siddiqui ◽  
Kazi Najamus-saqib Khan ◽  
Arafat Ali Farooqui ◽  
Muhammad Saad Farooqi ◽  
Muhammad Junaid Tariq ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Trial ◽  
Alkylating Agents ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Great Efficacy ◽  
Drug Regimens

Introduction: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) tend to have comorbidities and/or advanced age that make this subset of patients difficult to manage with current drug regimens. Methods: A comprehensive literature search of PubMed, Embase, Clinicaltrials.gov and Web of Science was performed from inception and completed on 07/17/2019. Studies focusing on efficacy and tolerability of 3-drug regimens in patients with NDMM were included for the review. Results: Out of 3579 studies, a total of 10 (08 phase II and 03 phase III) clinical trials in last ten years (2010-2019) using 3-drug regimens in NDMM elderly pts (893M/807F) ineligible for ASCT (determined by investigators) were selected. A total of 1703/1740 NDMM pts were evaluated. Proteasome inhibitors (PIs) such as carfilzomib (C), bortezomib (V) and ixazomib (I) showed promising results in elderly transplant-ineligible NDMM pts. CLARION trial (phase III, n=955) compared two PIs (C and V) with melphalan (M) and prednisone. There was no statistically significant difference in progression-free survival (PFS) between two groups (median: 22.3 vs 22.1 months; HR: 0.91; 95% CI, 0.75-1.10, p = 0.159) as well as overall survival (OS) (HR: 1.08; 95% CI: 0.82-1.43). Difference in the least square means of the HR-QoL (Health related- quality of life) was 4.99 (p<.0001) favoring C-group. M may not be an ideal drug to combine with carfilzomib in this setting given more AEs.(Facon et al 2019). V as 3-drug regimen in combination with lenalidomide (L) in 242 pts achieved statistically significant prolonged PFS (median 43 mo) and OS (median 75 mo) with great efficacy and acceptable risk-benefit profile. (Durie et al 2017; phase III). Multinational phase II trial (n=70) by Dimopoulos et al (2019) evaluated I, with different fixed doses of cyclophosphamide (Cy). Median duration was 19 cycles, indicating the long-term tolerability of regimen. With favorable toxicity profile and maintained QoL scores, trial concluded that this therapy is tolerable in elderly transplant-ineligible NDMM pts. Tuchman et al (2017) in phase II trial (n=14) investigated (V-Cy-d) and achieved ORR of 64%, with ≥VGPR of 57%. Low dose V showed great efficacy with M yielding ORR of 86% and VGPR or better of 49% in phase II trial (n=101) that also evaluated Cy as 3-drug combination but results were more productive with M with longer PFS and OS which reduced when impact of frailty was examined on outcomes. Since toxicity was higher with M, trial suggested that 2-drug combination should be preferred in elderly frail patients. (Larocca et al 2015). Efficacy was quite promising when Bringhen et al (2014) trialed C with Cy-d; 87% OS and 76% PFS at 1 y in phase II trial (n=58) with much favorable safety profile. Monoclonal antibodies (mAb) such as elotuzumab (E) and pembrolizumab (Pe) are also tested in elderly. First study conducted on NDMM pts using humanized mAb; E, in phase II trial (n=40) by Takezako et al (2017) attained primary endpoint of the study (ORR) of (88%) and VGPR or better of 45% in Japanese pts with tolerable toxicities in elderly. No subjects on this study experienced severe peripheral neuropathy. KEYNOTE-185; a phase III multinational trial by Usmani et al (2019) evaluated Pe with Ld in 151 pts. FDA halted this study due to unfavorable benefit-risk profile; 19 deaths, 6 due to disease progression (PD), and 13 due to treatment-related AEs. Median PFS and median OS were not reached in either group. Immunomodulators such as L achieved one of the longest PFS reported in a trial of transplant ineligible patients (35 mo) by using LVd regimen in phase II multicenter trial (n=50). (O'Donnell et al 2018) Alkylating agents like bendamustine (ben) and M have been tested in different novel regimens. Decreasing intensity and increasing duration of ben resulted in better outcomes in phase II trial (n=59) by Berdeja et al (2016) and can be given as first line treatment. Ben yielded great results with low dose dexa as compared to high dose achieving 92% ORR. Original regimen was effective but relatively more toxic. Incidence of herpes and neuropathy decreased dramatically with the treatment modifications. Conclusion: Three-drug regimens having PIs, mABs, immunomodulators and alkylating agents have shown desirable results in NDMM transplant (ASCT)-ineligible elderly patients and are likely the emerging standard of care for NDMM. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Abstract 14297: Potential Role of the Tumor Suppressor WWOX in Mediating Skeletal Muscle-Lung Vasculature Crosstalk in PH-HFpEF

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gunner Halliday ◽  
Yang Bai ◽  
Marta T Gomes ◽  
Dmitry Goncharov ◽  
Elena Goncharova ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tumor Suppressor ◽  
Potential Role ◽  
Pulmonary Vascular Remodeling ◽  
Expression Levels ◽  
Promote Cell Proliferation ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Group 2

Introduction: Pulmonary hypertension due to left heart disease (PH-LHD; Group 2), particularly in the context of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide. At present, no specific effective therapy has been identified mainly due to the fact that major pathways involved in the regulation of PH-HFpEF are still not well understood. Results: We have recently reported on a role of skeletal muscle sirtuin-3 (SIRT3) in modulating PH-HFpEF. Using skeletal muscle-specific SIRT3 knockout mice ( Sirt3 skm-/- ), we showed that absence of SIRT3 in skeletal muscle drastically reduced the pulmonary vascular tree accompanied by vascular proliferative remodeling. Interestingly, we found that expression levels of the tumor suppressor WW domain-containing oxidoreductase (WWOX) were decreased in pulmonary arterial smooth muscle cells (PASMCs) obtained from Sirt3 skm-/- mice, while no changes in SIRT3 activation levels were detected. Reduced WWOX expression levels were also found in PASMCs isolated from SU5416/Obese ZSF1 (Ob-Su) rat model of PH-HFpEF, in which the levels of SIRT3 activation were found to be decreased in skeletal muscle, but not in the lungs and PASMCs. No changes of WWOX levels were observed in skeletal muscle of Ob-Su rats or in pulmonary artery endothelial cells (PAECs) treated with plasma obtained from Ob-Su rats. Conclusions: Since reduction of WWOX in PASMCs has been shown to promote cell proliferation, HIF1α stabilization and pulmonary arterial hypertension (PAH; Group 1), our data suggest a potential role of WWOX in mediating skeletal muscle SIRT3 deficiency-associated remote pulmonary vascular remodeling in PH-HFpEF.

scholarly journals Transcriptional Regulation of Genes by Ikaros Tumor Suppressor in Acute Lymphoblastic Leukemia

2020 ◽  
Vol 21 (4) ◽  
pp. 1377
Author(s):  
Pavan Kumar Dhanyamraju ◽  
Soumya Iyer ◽  
Gayle Smink ◽  
Yevgeniya Bamme ◽  
Preeti Bhadauria ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tumor Suppressor ◽  
Chromatin Remodeling ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Lymphoblastic Leukemia ◽  
Regulatory Elements ◽  
Binding Motif ◽  
Functional Inactivation

Regulation of oncogenic gene expression by transcription factors that function as tumor suppressors is one of the major mechanisms that regulate leukemogenesis. Understanding this complex process is essential for explaining the pathogenesis of leukemia as well as developing targeted therapies. Here, we provide an overview of the role of Ikaros tumor suppressor and its role in regulation of gene transcription in acute leukemia. Ikaros (IKZF1) is a DNA-binding protein that functions as a master regulator of hematopoiesis and the immune system, as well as a tumor suppressor in acute lymphoblastic leukemia (ALL). Genetic alteration or functional inactivation of Ikaros results in the development of high-risk leukemia. Ikaros binds to the specific consensus binding motif at upstream regulatory elements of its target genes, recruits chromatin-remodeling complexes and activates or represses transcription via chromatin remodeling. Over the last twenty years, a large number of Ikaros target genes have been identified, and the role of Ikaros in the regulation of their expression provided insight into the mechanisms of Ikaros tumor suppressor function in leukemia. Here we summarize the role of Ikaros in the regulation of the expression of the genes whose function is critical for cellular proliferation, development, and progression of acute lymphoblastic leukemia.

Sign in / Sign up

Export Citation Format

Share Document