Marker In Leukemia Research Articles

107P Ultra-sensitive monitoring mutations in cancer patients using superRCA mutation detection assays

107P Ultra-sensitive monitoring mutations in cancer patients using superRCA mutation detection assays

Identification of cystic fibrosis transmembrane conductance regulator as a prognostic marker for juvenile myelomonocytic leukemia via the whole-genome bisulfite sequencing of monozygotic twins and data mining.

BackgroundLinked deoxyribonucleic acid (DNA) hypermethylation investigations of promoter methylation levels of candidate genes may help to increase the progressiveness and mortality rates of juvenile myelomonocytic leukemia (JMML), which is a unique myelodysplastic/myeloproliferative neoplasm caused by excessive monocyte and granulocyte proliferation in infancy/early childhood. However, the roles of hypermethylation in this malignant disease are uncertain.MethodsBone marrow samples from a JMML patient and peripheral blood samples from a healthy monozygotic twin and an unrelated healthy donor were collected with the informed consent of the participant’s parents. Whole-genome bisulfite sequencing (WGBS) was then performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to analyze specific differentially methylated region (DMG) related genes. The target genes were screened with Cytoscape and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), which are gene/protein interaction databases. A data mining platform was used to examine the expression level data of the healthy control and JMML patient tissues in Gene Expression Omnibus data sets, and a survival analysis was performed for all the JMML patients.ResultsThe STRING analysis revealed that the red node [i.e., the cystic fibrosis transmembrane conductance regulator (CFTR)] was the gene of interest. The gene-expression microarray data set analysis suggested that the CFTR expression levels did not differ significantly between the JMML patients and healthy controls (P=0.81). A statistically significant difference was observed in the CFTR promoter methylation level but not in the CFTR gene body methylation level. The overall survival analysis demonstrated that a high level of CFTR expression was associated with a worse survival rate in patients with JMML (P=0.039).ConclusionsCFTR promoter hypermethylation may be a novel biomarker for the diagnosis, monitoring of disease progression, and prognosis of JMML.

Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma.

Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a "resistance" parameter that reflects the stagnation in the response after an initial descent. Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P=.02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P=.02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.

Response to Letter to the Editor: IRF8 is a Reliable Monoblast Marker for Acute Monocytic Leukemias but does not Discriminate Between Monoblasts and Plasmacytoid Dendritic Cells.

Response to Letter to the Editor: IRF8 is a Reliable Monoblast Marker for Acute Monocytic Leukemias but does not Discriminate Between Monoblasts and Plasmacytoid Dendritic Cells.

Molecular genetic markers in acute myelogenous leukemia—the good, the bad, and the intermediate

Molecular genetic markers in acute myelogenous leukemia—the good, the bad, and the intermediate

A confirmation of ASXL1 as biological marker of normal cytogenetic acute myeloid leukemia with myelodysplasia-related changes (AML-MRC): A case successfully treated with CPX-351

We here report the case of a 56 yr old patient affected by acute myeloid leukemia with myelodisplasia related changes (AML‐MRC), ASXL1, successfully transplanted after CPX-351 treatment. Prats Martin et al.

Cell-free DNA 5-hydroxymethylcytosine is an emerging marker of acute myeloid leukemia

Aberrant changes in 5-hydroxymethylcytosine (5hmC) are a unique epigenetic feature in many cancers including acute myeloid leukemia (AML). However, genome-wide analysis of 5hmC in plasma cell-free DNA (cfDNA) remains unexploited in AML patients. We used a highly sensitive and robust nano-5hmC-Seal technology and profiled genome-wide 5hmC distribution in 239 plasma cfDNA samples from 103 AML patients and 81 non-cancer controls. We developed a 5hmC diagnostic model that precisely differentiates AML patients from controls with high sensitivity and specificity. We also developed a 5hmC prognostic model that accurately predicts prognosis in AML patients. High weighted prognostic scores (wp-scores) in AML patients were significantly associated with adverse overall survival (OS) in both training (P = 3.31e−05) and validation (P = 0.000464) sets. The wp-score was also significantly associated with genetic risk stratification and displayed dynamic changes with varied disease burden. Moreover, we found that high wp-scores in a single gene, BMS1 and GEMIN5 predicted OS in AML patients in both the training set (P = 0.023 and 0.031, respectively) and validation set (P = 9.66e−05 and 0.011, respectively). Lastly, our study demonstrated the genome-wide landscape of DNA hydroxymethylation in AML and revealed critical genes and pathways related to AML diagnosis and prognosis. Our data reveal plasma cfDNA 5hmC signatures as sensitive and accurate markers for AML diagnosis and prognosis. Plasma cfDNA 5hmC analysis will be an effective and minimally invasive tool for AML management.

P429: CLONALLY RESOLVED SINGLE-CELL MULTI-OMICS IDENTIFIES LEUKEMIA SURFACE ANTIGENS

Background: At the time of diagnosis, AML is a highly heterogeneous disease, usually consisting of various epigenetically and genetically distinct pre-leukemic, as well as leukemic subclones of various maturation stages that coexist in a competitive, or even cooperative manner. This clonal heterogeneity and, in particular, the strong resemblance of leukemic cells with their healthy counterparts presents a significant challenge in the identification of cancer specific gene expression and surface markers, both prerequisites for the development of targeted therapies. Existing approaches to add clonal resolution to droplet-based single-cell RNAseq data use qualitative information available from calls of individual mitochondrial or genomic single nucleotide variants as well as copy number variants. These single cell mutational calls, however, cannot be taken at face value, but need to be analysed through appropriate statistical methods, which are currently missing. Aims: Here we aimed at developing a novel method, CloneTracer, to add clonal resolution to new or existing human single-cell transcriptomic or multiomic datasets to ultimately allow identification of leukemia surface antigens through intra-sample comparison of cancerous and healthy cells of matched differentiation state. Methods: CloneTracer amplifies mitochondrial and selected nuclear SNVs, infers copy number variation, and estimates clonal hierarchies and identities through a Bayesian model that accounts for the noise properties of single-cell RNA-seq data. Results: Through combination of clonal identities with information on surface markers at single cell resolution, CloneTracer identified novel leukemia markers that enabled quantification of the leukemic burden in clinical specimens and enrichment for leukemic or healthy cells by FACS. Image:Summary/Conclusion: In summary, our data illustrate the benefits of clonally resolved single cell multi-omics for identifying cancer specific surface antigens and potential druggable targets by intra-patient comparisons.

Screening diagnostic markers for acute myeloid leukemia based on bioinformatics analysis.

BackgroundAn in-depth understanding of the key molecules and associated mechanisms involved in acute myeloid leukemia (AML) carcinogenesis, proliferation, and relapse is critical. This provides a basis for disease screening, early diagnosis, and development of effective treatment strategies and prognosis.MethodsWe downloaded AML transcription data sets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were screened by R software and limma packages. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on DEGs by public databases. In the DEG set, a random forest algorithm was used to identify characteristic genes of AML. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy of selected characteristic genes, which provided clues for the discovery of early diagnostic markers. The Estimate score was calculated using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. Spearman’s correlation test was used to explore the correlation between characteristic genes and Estimate Score, which provided clues for clarifying the potential pathogenic mechanism of key genes.ResultsA total of 1,494 DEGs were identified from AML samples and normal samples, among which 1,181 genes were upregulated and 313 genes were downregulated in AML. There were 2 genes with a mean decrease Gini >2, namely, CDC20 and ESM1, respectively. The ROC curve showed that the area under the curve (AUC) of CDC20 was 0.966, and the 95% confidence interval (CI) was (0.939 to 0.987) (P<0.001). The AUC of ESM1 was 0.905, and 95% CI: 0.849 to 0.953 (P<0.001). Correlation analysis showed that CDC20 expression was negatively correlated with Estimate Score (R=−0.21, P=0.0036) in AML. The expression of ESM1 was negatively correlated with Estimate Score (R=−0.57, P<0.001).ConclusionsThe genes CDC20 and ESM1 were identified as AML characteristic genes by random forest algorithm. Both CDC20 and ESM1 have good diagnostic efficacy for AML. They may play a carcinogenic role by promoting tumor cell proliferation and inhibiting immune cell chemotaxis, which are potential biological markers.

Evaluation of CDCP1 (CD318) and endoglin (CD105) expression as prognostic markers in acute myeloid leukemia.

The most commonly used prognostic factors in acute myeloid leukemia (AML) are cytogenetic, molecular, and morphological markers. However, AML prognosis is still unfavorable particularly in adults. So, further reliable markers are urgently needed to improve the risk stratification and treatment decisions. CUB domain-containing protein 1 (CDCP1; CD318) and endoglin (CD105) are new markers correlated with poor prognosis in different solid tumors, but their role in AML prognosis is not fully evaluated. This work aimed to evaluate the prognostic role of CD318 and CD105 in AML and their impact on the outcomes. Sixty-five newly diagnosed AML patients were included in this study. CD318 and CD105 expression was assessed by quantitative real-time polymerase chain reaction. Patients were followed up for ∼ 2 years to evaluate the prognostic impact of gene expression on the outcomes. Patients with high CD318 and CD105 showed higher white blood cell (WBC) count, M2 subtype, poor cytogenetic risk, reduced complete remission, and a greater number of deaths compared to low CD318 and CD105. CD318 was correlated with CD105, and both were correlated with WBC count, bone marrow blasts, and peripheral blood blasts. After a follow-up period of up to 24 months, relapse-free survival for high CD318 and CD105 was significantly different (42.1% and 52.6% vs. 64.5% and 58.1% for low CD318 and CD105, respectively). Survival was worse in patients with high CD318 and CD105, as the mean survival time was 13.9 and 13.3 months compared to 24 and 22.7 months in low CD318 and CD105, respectively. CD318 and CD105 are upregulated in AML patients. Their overexpression was associated with poor response to treatment and poor outcomes. Therefore, CD318 and CD105 can be useful prognostic markers in AML.

CNST is Characteristic of Leukemia Stem Cells and is Associated With Poor Prognosis in AML.

Consortin (CNST) is a protein located on the trans-Golgi network that can target transmembrane proteins to the plasma membrane. Although CNST was discovered more than 10 years ago, there are still not enough studies on its function. During our search for possible new acute myeloid leukemia (AML) markers, we found that CNST was overexpressed in almost all patients with AML. By analyzing profiling data from public databases, we found that CNST expression inversely correlated with overall survival among AML patients. There was a great variation in CNST expression among different subtypes of AML, and the expression was the highest in the t(8,21) subtype, which was probably due to the direct regulation of CNST transcription by RUNX1-RUNX1T1. In addition, we analyzed the expression of CNST in different cells of the hematopoietic system. We found that CNST was associated with the low differentiation degrees of hematopoietic cells and had the highest expression level in leukemia stem cells (LSCs). Finally, we analyzed the CNST-related gene network and found that the genes negatively correlated with CNST are involved in various immune-related pathways, which indicates that CNST is likely related to immune evasion, LSC niche retention, and assembly of stress granules. In conclusion, our study suggests that CNST has the potential to be a diagnostic and prognostic biomarker for AML.

WT1 Gene Mutations, rs16754 Variant, and WT1 Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients.

(1) Background: The aim of our study was the complex assessment of WT1 variants and their expression in relation to chromosomal changes and molecular prognostic markers in acute myeloid leukemia (AML). It is the first multidimensional study in Polish AML patients; (2) Methods: Bone marrow aspirates of 90 AML patients were used for cell cultures (banding techniques and fluorescence in situ hybridization), and to isolate DNA (WT1 genotyping, array comparative genomic hybridization), and RNA (WT1 expression). Peripheral blood samples from 100 healthy blood donors were used to analyze WT1 rs16754; (3) Results: Allele frequency and distribution of WT1 variant rs16754 (A;G) did not differ significantly among AML patients and controls. Higher expression of WT1 gene was observed in AA genotype (of rs16754) in comparison with GA or GG genotypes—10,556.7 vs. 25,836.5 copies (p = 0.01), respectively. WT1 mutations were more frequent in AML patients under 65 years of age (p < 0.0001) and affected relapse-free survival (RFS). The presence of NPM1 or CEBPA mutations decreased the risk of WT1 mutation presence, odds ratio (OR) = 0.11, 95% CI 0.02–0.46, p = 0.002 or OR = 0.05, 95% CI 0.006–0.46, p = 0.002, respectively. We observed significantly higher WT1 expression in AML CD34+ vs. CD34−, −20,985 vs. 8304 (p = 0.039), respectively. The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) Conclusions: WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML.

Serum hsa_circ_0079480 is a novel prognostic marker for acute myeloid leukemia.

BackgroundThe dysregulated expression of serum circular RNAs (circRNAs) has previously been linked to the prognosis of acute myeloid leukemia (AML) patients, but the clinical and prognostic relevance of serum hsa_circ_0079480 levels in this oncogenic setting have yet to be established. Herein, we assessed the putative prognostic relevance of circulating hsa_circ_0079480 levels in AML patient serum.MethodsSerum was prepared from blood samples collected from 236 AML patients and 160 healthy controls, with hsa_circ_0079480 levels therein being quantified by quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) after which the clinical value of these levels was assessed.ResultsAcute myeloid leukemia patients were found to exhibit significant hsa_circ_0079480 upregulation in their serum as compared to serum from healthy controls, with such upregulation being most profound in individuals with M4/M5 type disease and to be more common in patients with poor cytogenic risk or high white blood cell counts. Receiver operating characteristic (ROC) curves demonstrated that serum hsa_circ_0079480 levels were able to effectively differentiate between patients with AML and healthy controls. Moreover, the upregulation of serum hsa_circ_0079480 was found to be closely related to clinicopathological findings and to be an independent predictor of reduced overall and relapse‐free survival among individuals diagnosed with AML. Furthermore, serum hsa_circ_0079480 levels were markedly decreased after treatment in this patient population, with these levels being lower in patients that achieved complete remission as compared to those patients that did not.ConclusionLevels of hsa_circ_0079480 in patient serum may offer value as a prognostic biomarker in AML.

CIGB-300-Regulated Proteome Reveals Common and Tailored Response Patterns of AML Cells to CK2 Inhibition.

Protein kinase CK2 is a highly pleiotropic and ubiquitously expressed Ser/Thr kinase with instrumental roles in normal and pathological states, including neoplastic phenotype in solid tumor and hematological malignancies. In line with previous reports, CK2 has been suggested as an attractive prognostic marker and molecular target in acute myeloid leukemia (AML), a blood malignant disorder that remains as an unmet medical need. Accordingly, this work investigates the complex landscape of molecular and cellular perturbations supporting the antileukemic effect exerted by CK2 inhibition in AML cells. To identify and functionally characterize the proteomic profile differentially modulated by the CK2 peptide-based inhibitor CIGB-300, we carried out LC-MS/MS and bioinformatic analysis in human cell lines representing two differentiation stages and major AML subtypes. Using this approach, 109 and 129 proteins were identified as significantly modulated in HL-60 and OCI-AML3 cells, respectively. In both proteomic profiles, proteins related to apoptotic cell death, cell cycle progression, and transcriptional/translational processes appeared represented, in agreement with previous results showing the impact of CIGB-300 in AML cell proliferation and viability. Of note, a group of proteins involved in intracellular redox homeostasis was specifically identified in HL-60 cell-regulated proteome, and flow cytometric analysis also confirmed a differential effect of CIGB-300 over reactive oxygen species (ROS) production in AML cells. Thus, oxidative stress might play a relevant role on CIGB-300-induced apoptosis in HL-60 but not in OCI-AML3 cells. Importantly, these findings provide first-hand insights concerning the CIGB-300 antileukemic effect and draw attention to the existence of both common and tailored response patterns triggered by CK2 inhibition in different AML backgrounds, a phenomenon of particular relevance with regard to the pharmacologic blockade of CK2 and personalized medicine.

Pathogenetic Significance of YBX1 Expression in Acute Myeloid Leukemia Relapse

BackgroundGenomic abnormalities were established as prognostic and diagnostic markers for acute myeloid leukemia (AML) tumorgenesis and YBX1 gene has important roles in different cancer types. MethodsA total of 109 adult and pediatric patients with De novo AML, were enrolled in this study. Besides the routine lab work; bone marrow YBX1 expression levels were measured using qRT-PCR, and then its possible connections to AML pathogenesis pathway were investigated by STRING tool. ResultsResults demonstrated upregulation of YBX1 expression level in AML patients that was associated with the presence of adverse genomics abnormalities. In adult patients, the level of YBX1 expression was significantly high in relapsed and resistant groups, while in pediatric patients, the level of YBX1 expression showed an inverse pattern as it was highly expressed in complete remission group. STRING analysis highlighted that YBX1 interacts with important factors in the AML signaling pathway. Kaplan-Meier analysis indicated that adult patients with highly expressed YBX1 significantly endured shorter disease-free survival (DFS) compared to low YBX1 expressers and there was no impact of YBX1 on adult patients overall survival (OS). While pediatric patients with upregulated YBX1 showed good OS over downregulated patients. ConclusionIn conclusion, YBX1 may have a crucial role in AML relapse pathogenesis. Also, it could serve as a prognostic factor for AML disease outcomes.

EP053: Detection of rare and novel fusions in pediatric B-Lymphoblastic Leukemia (B-ALL) by capture-based transcriptome sequencing (RNA-Seq)

Numerous newly recognized clinically significant genetic markers in B-lymphoblastic leukemia (B-ALL) that are being incorporated into the next edition of the World Health Organization (WHO) classification cannot be detected by routine karyotype and fluorescence in situ hybridization (FISH) analyses. For example, EPOR and CRLF2 rearrangements associated with the BCR-ABL1 (Philadelphia)-like subtype of B-ALL and abnormalities which define DUX4-upregulated subtype of the disease, remain undetected by standard cytogenetic evaluation.

Cell surface expression of GRP78 and CXCR4 is associated with childhood high-risk acute lymphoblastic leukemia at diagnostics

Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GRP78 (sGRP78) is expressed on cancer cells but not in normal cells. Here, we explored the presence of sGRP78 in pediatric B-ALL at diagnosis and investigated the correlation with bona fide markers of leukemia. By using a combination of flow cytometry and high multidimensional analysis, we found a distinctive cluster containing high levels of sGRP78, CD10, CD19, and CXCR4 in bone marrow samples obtained from High-risk leukemia patients, which was absent in the compartment of Standard-risk leukemia. We confirmed that sGRP78+CXCR4+ blood-derived cells were more frequent in High-risk leukemia patients. Finally, we analyzed the dissemination capacity of sGRP78 leukemia cells in a model of xenotransplantation. sGRP78+ cells emigrated to the bone marrow and lymph nodes, maintaining the expression of CXCR4. Testing the presence of sGRP78 and CXCR4 together with conventional markers may help to achieve a better categorization of High and Standard-risk pediatric leukemia at diagnosis.

Aberrant expression of myeloid antigens in patients of acute lymphoblastic leukaemia.

To determine the immunophenotypic pattern and aberrant expression of myeloid antigens in newly diagnosed patients of acute lymphoblastic leukaemia(ALL). This descriptive cross-sectional study was carried out in Haematology / Pathology department, Army Medical College, National University of Medical Sciences (NUMS) in collaboration with Immunology and Haematology departments of Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January, 2019 to 31st December, 2019. Seventy-three (73) recently diagnosed patients of Acute Lymphoblastic leukaemia of all age groups and both genders were included in the study. A proforma was used to note demographic data. CBC, cytochemical stains and bone marrow examinations were carried out and assessed for morphology and percentage of blasts using a microscope. Flow cytometry was used to perform immunophenotyping on samples of peripheral blood and bone marrow, using a standard panel. The most commonly expressed markers were weak CD45, TdT, CD19, CD10 and HLA-DR. Weak CD45 was present in almost all blast cells and there was no remarkable difference in its positivity among various subtypes of ALL. Myeloid expression was observed in 13 (17.8%) cases. CD13 and CD33 were aberrantly expressed in 11 and 12.3 of all cases of ALL respectively. Expression of aberrant myeloid CD markers in acute lymphocytic leukaemia has prognostic significance and should be documented during lineage assignment of acute leukaemias while performing immunophenotyping.

Negative value of CD10-/CD34- immunophenotype in pediatric leukemia and development of a related cell line model for investigating drug resistance.

Appropriate sub-classification of leukemia according to the immunophenotypic characteristics of the malignant cells may improve therapeutic strategies. The aim of this study was to investigate the prognostic value of CD10/CD34 surface markers in pediatric acute lymphoblastic leukemia (pALL). A retrospective cohort study was performed in 79 children with ALL. Possible correlation between leukemia prognosis and CD10 CD34 immunophenotype was assessed using Kaplan-Meier and Cox regression analyses. A CD10- CD34- pre-B-ALL cell line was generated from a patient with resistant ALL. RN95 was characterized using light microscopy, immunophenotyping, karyotyping, and Western blotting. Drug sensitivity and resistant genes' expression profile were assessed using MTT and RT-PCR assays. Kaplan-Meier analysis showed negative correlation between CD10/CD34 double negativity and patients' 2- and 5-year disease-free survival (DFS). Multivariate analysis indicated that the absence of CD10 and CD34 expression in the ALL patients was an independent negative prognostic marker for 2- and 5-year DFS. A novel cell line model, RN95, was developed with similar immunophenotype from a primary relapsed sample. Cells showed p53 positive functionality and demonstrated partial sensitivity to Vincristine, but complete resistance to Cytarabine. Overexpression of ABCB1, ABCA2, and ABCA3 was detected. In the current study, simultaneous absence of CD10 and CD34 cell surface markers was introduced as an unfavorable prognostic factor in pediatric B-ALL. Moreover, a special cell line was established to help delineation of novel therapeutics for B-ALL drug resistance.

Plasmacytoma Variant Translocation-1 as Prognostic Markers in Pediatric Acute Lymphoblastic Leukemia

Introduction and Aim: Acute lymphoblastic leukemia (ALL) is the commonest form of childhood leukemia. Molecular studies can provide diagnostic and prognostic information with direct impact on the patient. Recent micro RNAs (miRNAs) studies showed that aberrant expression can be used as signatures of ALL with different subtypes and predict drug resistance. The present work aimed to evaluate the expression of Plasmacytoma Variant Translocation-1 (PVT1) in Childhood ALL patients.&#x0D; Methodology: The study included 55 children from 2 months to 15 years old; 45 patients with ALL before receiving any treatment, and 10 control children. Long non-coding RNA PVT1 expression in plasma cells was detected by reverse transcription quantitative polymerase chain reaction.&#x0D; Results: Lnc_PVT1 expression is upregulated by twelve-folds in ALL patients. At optimum cut-off value of 22.0, the biomarker has a sensitivity of 72% and 82% specificity to discriminate ALL patients from controls. Correlating the mean values of miR_1204gene fold expression with different subgroups concerning prognostic criteria, there was no statistical differences between age groups, gender, ALL phenotypes, cytogenetic abnormality, total leukocytes count, hemoglobin concentrations and platelet count. In contrast, statistical significance was detected with bone marrow blasts percentage, clinical response, and minimal residual disease.&#x0D; Conclusion: A higher expression of lnc-PVT1 was observed in ALL patients, and it had a diagnostic and prognostic potential. In addition, miR-1204 was down-regulated in pediatric ALL and associated with higher risk.