scholarly journals A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Siobhan Rice ◽  
Thomas Jackson ◽  
Nicholas T. Crump ◽  
Nicholas Fordham ◽  
Natalina Elliott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Fetal Liver ◽  
Lymphoblastic Leukemia ◽  
Disease Model ◽  
Driver Mutations ◽  
Specific Gene ◽  
Childhood All ◽  
Human Fetal Liver ◽  
Specific Gene Expression

AbstractAlthough 90% of children with acute lymphoblastic leukemia (ALL) are now cured, the prognosis for infant-ALL remains dismal. Infant-ALL is usually caused by a single genetic hit that arises in utero: an MLL/KMT2A gene rearrangement (MLL-r). This is sufficient to induce a uniquely aggressive and treatment-refractory leukemia compared to older children. The reasons for disparate outcomes in patients of different ages with identical driver mutations are unknown. Using the most common MLL-r in infant-ALL, MLL-AF4, as a disease model, we show that fetal-specific gene expression programs are maintained in MLL-AF4 infant-ALL but not in MLL-AF4 childhood-ALL. We use CRISPR-Cas9 gene editing of primary human fetal liver hematopoietic cells to produce a t(4;11)/MLL-AF4 translocation, which replicates the clinical features of infant-ALL and drives infant-ALL-specific and fetal-specific gene expression programs. These data support the hypothesis that fetal-specific gene expression programs cooperate with MLL-AF4 to initiate and maintain the distinct biology of infant-ALL.

scholarly journals A novel human fetal liver-derived model reveals that MLL-AF4 drives a distinct fetal gene expression program in infant ALL

2020 ◽  
Author(s):  
Siobhan Rice ◽  
Thomas Jackson ◽  
Nicholas T Crump ◽  
Nicholas Fordham ◽  
Natalina Elliott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Lymphoblastic Leukemia ◽  
Driver Mutations ◽  
Specific Gene ◽  
Older Children ◽  
Childhood All ◽  
Human Fetal Liver ◽  
Specific Gene Expression ◽  
First Year Of Life

ABSTRACTAlthough 90% of children with acute lymphoblastic leukemia (ALL) are now cured1, the prognosis of infant-ALL (diagnosis within the first year of life) remains dismal2. Infant-ALL is usually caused by a single genetic hit that arises in utero: rearrangement of the MLL/KMT2A gene (MLL-r). This is sufficient to give rise to a uniquely aggressive and treatment-refractory leukemia compared to older children with the same MLL-r3–5. The reasons for disparate outcomes in patients of different ages with identical driver mutations are unknown. This paper addresses the hypothesis that fetal-specific gene expression programs co-operate with MLL-AF4 to initiate and maintain infant-ALL. Using direct comparison of fetal and adult HSC and progenitor transcriptomes we identify fetal-specific gene expression programs in primary human cells. We show that MLL-AF4-driven infant-ALL, but not MLL-AF4 childhood-ALL, displays expression of fetal-specific genes. In a direct test of this observation, we find that CRISPR-Cas9 gene editing of primary human fetal liver cells to produce a t(4;11)/MLL-AF4 translocation replicates the clinical features of infant-ALL and drives infant-ALL-specific and fetal-specific gene expression programs. These data strongly support the hypothesis that fetal-specific gene expression programs co-operate with MLL-AF4 to initiate and maintain the distinct biology of infant-ALL.

scholarly journals Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5201-5210 ◽  
Author(s):  
Teena Bhatla ◽  
Jinhua Wang ◽  
Debra J. Morrison ◽  
Elizabeth A. Raetz ◽  
Michael J. Burke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Dna Methyltransferase ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Gene Expression Signature ◽  
Specific Gene ◽  
Epigenetic Mechanisms ◽  
Specific Gene Expression ◽  
Aberrant Gene

Whereas the improvement in outcome for children with acute lymphoblastic leukemia has been gratifying, the poor outcome of patients who relapse warrants novel treatment approaches. Previously, we identified a characteristic relapse-specific gene expression and methylation signature associated with chemoresistance using a large cohort of matched-diagnosis relapse samples. We hypothesized that “reversing” such a signature might restore chemosensitivity. In the present study, we demonstrate that the histone deacetylase inhibitor vorinostat not only reprograms the aberrant gene expression profile of relapsed blasts by epigenetic mechanisms, but is also synergistic when applied before chemotherapy in primary patient samples and leukemia cell lines. Furthermore, incorporation of the DNA methyltransferase inhibitor decitabine led to reexpression of genes shown to be preferentially methylated and silenced at relapse. Combination pretreatment with vorinostat and decitabine resulted in even greater cytotoxicity compared with each agent individually with chemotherapy. Our results indicate that acquisition of chemo-resistance at relapse may be driven in part by epigenetic mechanisms. Incorporation of these targeted epigenetic agents to the standard chemotherapy backbone is a promising approach to the treatment of relapsed pediatric acute lymphoblastic leukemia.

Folate Pathway Gene Expression Differs in Genetic Subtypes of Acute Lymphoblastic Leukemia and Influences Methotrexate Pharmacodynamics.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 452-452
Author(s):  
Leo Kager ◽  
Meyling H. Cheok ◽  
Wenjian Yang ◽  
Gianluigi Zaza ◽  
Ching-Hon Pui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cells ◽  
Cancer Resistance ◽  
Childhood All ◽  
Pathway Gene ◽  
Folate Pathway ◽  
B Lineage ◽  
Lower Expression

Abstract Methotrexate (MTX) is an essential treatment component for acute lymphoblastic leukemia (ALL). The ability of leukemia cells to accumulate MTX in its polyglutamylated form (MTXPG) is recognized as an important determinant of its antileukemic effect. We measured in vivo MTXPG accumulation in leukemia cells from 101 children with ALL, and established that blasts of B-lineage ALL with either the TEL-AML1 (n=24 patients, median 911, range 338 to 5906 pmol/109 blasts) or E2A-PBX1 gene fusion (n=5, median 553, range 364 to 800 pmol/109 blasts) or T-lineage ALL (n=14, median 572, range 284 to 1468 pmol/109 blasts) accumulate significantly lower MTXPG, compared to those of other B-lineage ALL (BNHD, n=39, median 2210, range 186 to 9722 pmol/109 blasts) or hyperdiploid ALL (BHD, n=19, median 4375, range 377 to 9206 pmol/109 blasts) (E2A-PBX1 versus BHD, p=0.008; E2A-PBX1 vs. BNHD, p=0.010; TEL-AML1 vs. BHD, p<0.001; TEL-AML1 vs. BNHD, p=0.004; T-ALL vs. BHD and BNHD, p<0.001; p-values are from pair-wise comparisons using Wilcoxon rank sum test, adjusted for multiple testing using Holm’s method). To elucidate mechanisms underlying these differences in MTXPG accumulation, we used oligonucleotide microarrays (Affymetrix® HG-U133A) to analyze expression of 32 folate pathway genes (53 probe sets) in diagnostic bone marrow blasts from 197 children with ALL. This revealed ALL subtype-specific patterns of folate metabolism gene expression and identified differences in gene expression that discriminated the MTXPG accumulation phenotype in ALL cells. We found significantly lower expression of the reduced folate carrier (SLC19A1, MTX uptake transporter) in E2A-PBX1 ALL; significantly higher expression of breast cancer resistance protein (ABCG2, MTX efflux transporter) in TEL-AML1 ALL; and lower expression of FPGS (catalyzes formation of MTXPG) in T-ALL; consistent with lower MTXPG accumulation in these ALL subtypes. These findings reveal distinct mechanisms of subtype-specific differences in MTXPG accumulation and point to new strategies to overcome this potential cause of treatment failure in childhood ALL.

Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 821-826 ◽  
Author(s):  
Gunnar Cario ◽  
Martin Stanulla ◽  
Bernard M. Fine ◽  
Oliver Teuffel ◽  
Nils v. Neuhoff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Treatment Response ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Treatment Resistance ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Childhood All ◽  
Resistance To Chemotherapy ◽  
Intrinsic Feature

AbstractTreatment resistance, as indicated by the presence of high levels of minimal residual disease (MRD) after induction therapy and induction consolidation, is associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL). We hypothesized that treatment resistance is an intrinsic feature of ALL cells reflected in the gene expression pattern and that resistance to chemotherapy can be predicted before treatment. To test these hypotheses, gene expression signatures of ALL samples with high MRD load were compared with those of samples without measurable MRD during treatment. We identified 54 genes that clearly distinguished resistant from sensitive ALL samples. Genes with low expression in resistant samples were predominantly associated with cell-cycle progression and apoptosis, suggesting that impaired cell proliferation and apoptosis are involved in treatment resistance. Prediction analysis using randomly selected samples as a training set and the remaining samples as a test set revealed an accuracy of 84%. We conclude that resistance to chemotherapy seems at least in part to be an intrinsic feature of ALL cells. Because treatment response could be predicted with high accuracy, gene expression profiling could become a clinically relevant tool for treatment stratification in the early course of childhood ALL.

High Rate of FLT3 Mutations In Adult ETP-ALL.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1031-1031 ◽  
Author(s):  
Martin Neumann ◽  
Ebru Coskun ◽  
Ouidad Benlasfer ◽  
Sandra Heesch ◽  
Stefan Schwartz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Expression Pattern ◽  
Mirna Expression ◽  
Lymphoblastic Leukemia ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Gene Expression ◽  
Flt3 Mutation ◽  
Flt3 Mutations

Abstract Abstract 1031 Introduction: Mutations of FLT3 are recognized as important prognostic factor in acute myeloid leukemia (AML) with an impact on new therapeutic strategies. However, FLT3 mutations are rarely (1-3%) found in acute T-lymphoblastic leukemia (T-ALL). Recently, a new T-ALL subgroup defined by a specific gene expression profile and a characteristic immunophenotype (CD1a-, CD8-, CD5weak with expression of stem cell or myeloid markers) and with poor outcome has been described in pediatric T-ALL patients. This subgroup likely originates from early thymic progenitors (ETP) and has therefore been termed ETP-ALL. To unravel the molecular alterations of this distinct subgroup with myeloid characteristics, we studied adult ETP-ALL patients for FLT3 mutations. Moreover, we analyzed miRNA expression to explore their potential involvement in the specific gene expression signature observed in ETP-ALL. Patients and methods: We screened 1241 peripheral blood and bone marrow samples of T-ALL patients that were sent to the central diagnostic reference laboratory of the German Acute Lymphoblastic Leukemia Multicenter Study Group (GMALL). Of the immunophenotypically identified ETP-ALL patients (n=142), sufficient material was available in 70 cases. FLT3 mutations (ITD and TKD) were assessed using the FLT3 mutation assay (InVivoScribe Technologies, San Diego, USA). Expression of miRNAs was first screened by TaqMan low density arrays including 667 miRNAs in ETP-ALL (n=8) and compared to non-ETP T-ALL (n=6). Subsequently, expression of miR-221 and miR-222 was examined by real-time PCR in all 70 ETP-ALL. Results: In our cohort of 1241 T-ALL, 142 (11.4 %) patients showed an immunophenotype of an ETP-ALL, which is in the range of reported frequencies in pediatric patients. Among the 70 ETP-ALL samples analyzed, we identified 9 patients with a FLT3 D835 mutation and 15 patients with a FLT3 ITD. In total, 34 % (24 of the 70) patients carried a FLT3 mutation, which represents approximately 4 % of all T-ALL patients. In contrast, only one patient was identified with a FLT3 mutation within an arbitrarily selected control group of 107 T-ALL patients with a non-ETP immunophenotype. Interestingly, ETP-ALL with FLT3 mutations showed a distinct immunophentype compared to ETP-ALL with a wild type FLT3: ETP-ALL with FLT3 mutations had a higher rate of positivity for CD2 (88% vs. 30%, P<0.001), CD117 (83% vs. 28%, P<0.001), and CD13 (100 % vs. 37%, P<0.001). On the other hand, ETP-ALL with wild type FLT3 were characterized by a more frequent positivity of CD5 (54% vs. 4%, P<0.001) and CD33 (54% vs. 4%, P<0.001). Based on these findings a specific immunophenotype may be linked to FLT3 mutated ETP-ALL: in 73% (21/29) of patients with CD2/CD13 positivity a FLT3 mutation was present, compared to only 7% (3/41) of the remaining patients with ETP-ALL. In addition, we generated miRNA expression profiles in ETP-ALL and identified 7 miRNAs that were differentially expressed compared to non-ETP T-ALL. Among these miR-221 and miR-222, which were significantly overexpressed in ETP-ALL, are targeting genes characterizing the ETP-ALL phenotype (e.g. ETS1, KIT). Examination of miR-221 and miR-222 in 70 ETP-ALL revealed their particular overexpression in FLT3 mutated samples (miR-221 2.45-fold, P=0.012; miR-222: 2.05-fold, P=0.008) compared to ETP-ALL with wild type FLT3. Conclusion: We identified a yet unreported high frequency of FLT3 mutations in T-ALL, which are nearly exclusively found within the subgroup of ETP-ALL. In this group the rate is comparable high to the rate of FLT3 mutations in AML. Therefore, on the basis of established flow cytometry analysis we identified T-ALL patients that should be now prospectively and routinely screened for FLT3 mutations. Moreover, the distinct miRNA expression pattern may impact on the specific gene expression pattern of ETP-ALL. Thus, patients of this molecular distinct ETP-ALL entity may benefit from tyrosine kinase inhibitors in relapse situations or with presence of minimal residual disease as a bridging therapy to allogeneic stem cell transplantation. Disclosures: Baldus: Novartis: Research Funding.

scholarly journals Organ-Specific Gene Expression Changes in the Fetal Liver and Placenta in Response to Maternal Folate Depletion

Nutrients ◽  
2016 ◽  
Vol 8 (10) ◽  
pp. 661 ◽  
Author(s):  
Jill McKay ◽  
Long Xie ◽  
Michiel Adriaens ◽  
Chris Evelo ◽  
Dianne Ford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Organ Specific ◽  
Folate Depletion

scholarly journals Expression of telomeric repeat binding factor 2 (TERF2) in childhood acute lymphoblastic leukemia

2021 ◽  
pp. 98-106
Author(s):  
Lelamekala Vengidasan ◽  
Choong Soo Sin ◽  
Chen Kok Siong ◽  
Kamariah Ibrahim
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Internal Control ◽  
Lymphoblastic Leukemia ◽  
Prognostic Indicator ◽  
Good Prognosis ◽  
P Value ◽  
Childhood All ◽  
Over Expression ◽  
Main Components

Acute lymphoblastic leukemia (ALL) is the most frequent cancer among children. Regardless of the advances in disease treatments, approximately 10-20 % of childhood ALL (cALL) have an incidence of relapse. Therefore, identification of additional prognostic variables is essential to provide specific therapeutic intervention for each patient. TERF2 is one of the main components of the shelterin complex (telosome) that plays a crucial role in the protective activity of telomeres. This research aims to investigate the expression level of TERF2 and its potential as a prognostic marker in cALL patients. 88 bone marrow samples and 6 peripheral blood were used to isolated cDNA samples. Real time PCR were used to study the gene expression of TERF2 in cALL. Results were standardized using B2M transcripts as an internal control. Relative quantification of the gene expression was calculated by using the delta-delta Ct method. TERF2 was up-regulated significantly in cALL patients compared to control samples of which p-value=0.002859, (p<0.05). Over-expression of TERF2 was observed in TEL-AML1 subgroup of which p-value=0.0002, (p<0.05). In contrast, under-expression of TERF2 was found in those having BCR-ABL1 fusion transcripts of which p-value=0.0221, (p<0.05). TERF2 also have found to have a better survival advantages for cALL patients. Over-expression of TERF2 is associated with good prognosis in cALL whilst under-expression is associated with poor prognosis in cALL patients. Measurement of TERF2 gene expression allows proper stratification of cALL subtypes into its respective prognostic indicator classification.

Gene expression–based classification and regulatory networks of pediatric acute lymphoblastic leukemia

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4486-4493 ◽  
Author(s):  
Zhigang Li ◽  
Wei Zhang ◽  
Minyuan Wu ◽  
Shanshan Zhu ◽  
Chao Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Patient Group ◽  
Regulatory Networks ◽  
Lymphoblastic Leukemia ◽  
Expression Patterns ◽  
Independent Set ◽  
Specific Gene ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Disease Subtype

Abstract Pediatric acute lymphoblastic leukemia (ALL) contains cytogenetically distinct subtypes that respond differently to cytotoxic drugs. Subtype classification can be also achieved through gene expression profiling. However, how to apply such classifiers to a single patient and correctly diagnose the disease subtype in an independent patient group has not been addressed. Furthermore, the underlying regulatory mechanisms responsible for the subtype-specific gene expression patterns are still largely unknown. Here, by combining 3 published microarray datasets on 535 mostly white children's samples and generating a new dataset on 100 Chinese children's ALL samples, we were able to (1) identify a 62-gene classifier with 97.6% accuracy from the white children's samples and validated it on the completely independent set of 100 Chinese samples, and (2) uncover potential regulatory networks of ALL subtypes. The classifier we identified was, thus far, the only one that could be applied directly to a single sample and that sustained validation in a large independent patient group. Our results also suggest that the etiology of ALL is largely the same among different ethnic groups, and that the transcription factor hubs in the predicted regulatory network might play important roles in regulating gene expression and development of ALL.

Comparative Analysis of Gene Expression Profiles between Diagnosis and Relapse of Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2809-2809
Author(s):  
Tomasz Szczepanski ◽  
Dick de Ridder ◽  
Vincent H.J. van der Velden ◽  
Tom Schonewille ◽  
Elisabeth van Wering ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Gene Expression Profiles ◽  
Detailed Comparison ◽  
Cell Precursor ◽  
Childhood All

Abstract Approximately 30% of childhood acute lymphoblastic leukemia (ALL) patients relapse, which is the most frequent adverse event in this otherwise curable disease. The mechanisms of relapse are largely unknown. Earlier studies indicated that some relapses might originate from subclones with many different biological features compared to the original ALL clones at diagnosis. Therefore, we aimed at detailed comparison of gene expression profiles between diagnosis and relapse of childhood ALL. The study group consisted of 41 children, 27 diagnosed with B-cell precursor ALL (BCP-ALL) and 14 with T-cell precursor ALL (T-ALL). All samples obtained at diagnosis and relapse were subjected to purification using CliniMACS system and enriched to more than 95% of blasts in each sample. RNA isolation and gene expression profiling were performed according to standard procedures using Affymetrix HG-U133+2 set GeneChip arrays (Affymetrix). The samples were also screened at the RNA level for the most common genetic aberrations occurring in ALL such as t(9;22), t(4;11), t(12;21) and TAL1 deletion. The studies at the DNA level involved detailed comparison of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements between diagnosis and relapse to assess clonal evolution. GeneChip array data were quantile normalized and background was removed using robust multichip analysis. Significance Analysis of Microarrays (SAM) and t-test were applied to find differentially expressed probe sets between diagnosis and relapse using both the paired and unpaired criterion. The p values < 0.05 were considered significant. The paired SAM analysis revealed 388 significantly differentially expressed (SDE) probe sets for BCP-ALL and 10 SDE probe sets for T-ALL. The differences in expression levels were relatively low, generally not exceeding two-fold. SDE gene sets revealed in our study were mainly different from previously published data, which is most probably due to more stringent purification procedures. Using Ingenuity Systems the SDE genes in BCP-ALL could be significantly linked to several networks involved in cell cycle, DNA replication, recombination, and repair, cellular assembly and organization, cellular growth, proliferation and cancer. There were no significant differences in gene expression profiling in smaller immunophenotypic and cytogenetic ALL subgroups as well as in relation to remission duration (early vs. late relapse). Several SDE genes were found when comparing the ALL with stable Ig/TCR configuration and with some clonal evolution (22 probes for T-ALL and 8 probes for BCP-ALL). In conclusion, discrete differences of gene expression profiles between diagnosis and relapse of childhood ALL indicate heterogeneous origin of relapse. Many relapses represent the simple outgrowth of the original clone, while in other cases many different (leukemia-related) relapse mechanisms might be involved.

High Interleukin-15 Expression Characterizes Childhood Acute Lymphoblastic Leukemia With Involvement of the CNS

2007 ◽  
Vol 25 (30) ◽  
pp. 4813-4820 ◽  
Author(s):  
Gunnar Cario ◽  
Shai Izraeli ◽  
Anja Teichert ◽  
Peter Rhein ◽  
Julia Skokowa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Gene Expression Profiles ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Cns Involvement ◽  
Childhood All ◽  
Interleukin 15

Purpose Applying current diagnostic methods, overt CNS involvement is a rare event in childhood acute lymphoblastic leukemia (ALL). In contrast, CNS-directed therapy is essential for all patients with ALL because without it, the majority of patients eventually will experience relapse. To approach this discrepancy and to explore potential distinct biologic properties of leukemic cells that migrate into the CNS, we compared gene expression profiles of childhood ALL patients with initial CNS involvement with the profiles of CNS-negative patients. Patients and Methods We evaluated leukemic gene expression profiles from the bone marrow of 17 CNS-positive patients and 26 CNS-negative patients who were frequency matched for risk factors associated with CNS involvement. Results were confirmed by real-time quantitative polymerase chain reaction analysis and validated using independent patient samples. Results Interleukin-15 (IL-15) expression was consistently upregulated in leukemic cells of CNS-positive patients compared with CNS-negative patients. In multivariate analysis, IL-15 expression levels greater than the median were associated with CNS involvement compared with expression equal to or less than the median (odds ratio [OR] = 10.70; 95% CI, 2.95 to 38.81). Diagnostic likelihood ratios for CNS positivity were 0.09 (95% CI, 0.01 to 0.65) for the first and 6.93 (95% CI, 2.55 to 18.83) for the fourth IL-15 expression quartiles. In patients who were CNS negative at diagnosis, IL-15 levels greater than the median were associated with subsequent CNS relapse compared with expression equal to or less than the median (OR = 13.80; 95% CI, 3.38 to 56.31). Conclusion Quantification of leukemic IL-15 expression at diagnosis predicts CNS status and could be a new tool to further tailor CNS-directed therapy in childhood ALL.

Sign in / Sign up

Export Citation Format

Share Document