MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.

In the past decade, significant advances in molecular research have provided a deeper understanding of the intricate regulatory mechanisms involved in carcinogenesis. MicroRNAs, short non-coding RNA sequences, exert substantial influence on gene expression by repressing translation or inducing mRNA degradation. In the context of cancer, miRNA dysregulation is prevalent and closely associated with various stages of carcinogenesis, including initiation, progression, and metastasis. One crucial aspect of the cancer phenotype is the activity of histone-modifying enzymes that govern chromatin accessibility for transcription factors, thus impacting gene expression. Recent studies have revealed that miRNAs play a significant role in modulating these histone-modifying enzymes, leading to significant implications for genes related to proliferation, differentiation, and apoptosis in cancer cells. This article provides an overview of current research on the mechanisms by which miRNAs regulate the activity of histone-modifying enzymes in the context of cancer. Both direct and indirect mechanisms through which miRNAs influence enzyme expression are discussed. Additionally, potential therapeutic implications arising from miRNA manipulation to selectively impact histone-modifying enzyme activity are presented. The insights from this analysis hold significant therapeutic promise, suggesting the utility of miRNAs as tools for the precise regulation of chromatin-related processes and gene expression. A contemporary focus on molecular regulatory mechanisms opens therapeutic pathways that can effectively influence the control of tumor cell growth and dissemination.

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA.

Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.

MicroRNA as a Potential Therapeutic Molecule in Cancer.

Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated the potential to sensitize cancer cells to therapy. Their properties of modulating the response of cells to therapy have made them a promising target for overcoming drug resistance. Several methods have been developed for the delivery of miRNAs to cancer cells, including introducing synthetic miRNA mimics, DNA plasmids containing miRNAs, and small molecules that epigenetically alter endogenous miRNA expression. The results of studies in animal models and preclinical studies for solid cancers and hematological malignancies have confirmed the effectiveness of treatment protocols using microRNA. Nevertheless, the use of miRNAs in anticancer therapy is not without limitations, including the development of a stable nanoconstruct, delivery method choices, and biodistribution. The aim of this review was to summarize the role of miRNAs in cancer treatment and to present new therapeutic concepts for these molecules. Supporting anticancer therapy with microRNA molecules has been verified in numerous clinical trials, which shows great potential in the treatment of cancer.

Analysis of profibrogenic microRNAs (miRNAs) expression in urine and serum of chronic kidney disease (CKD) stage 1-4 patients and their relationship with proteinuria and kidney function.

PURPOSE: Besides conventional kidney diseases diagnostics, micro RNAs (miRNAs) assessment in urine and serum is considered to be a promising non-invasive method of diagnostics of renal parenchymal diseases and valuable therapeutic target also. The purpose of the study was to investigate the role of several miRNAs as a markers of kidney damage. METHODS: Assessment of 45 chronic kidney disease (CKD) patients stage 1-4 and 17 healthy control. Sample of urine and blood was taken from each participant for molecular analysis using Real Time PCR method to identify such micro-RNAs as: hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-200a-5p, hsa-miR-29a-5p, hsa-miR-21-5p, hsa-miR-93-5p, and hsa-miR-196a-5p. Basic biochemical test was done. Analysis was performed in CKD patients group and subgroup with chronic glomerulonephritis (CGN) confirmed by kidney biopsy. Moreover, analysis was performed in subgroup with different estimated glomerular filtration rate (eGFR) (according to CKD-EPI equation: eGFR < 60 ml/min, eGFR > 60 ml/min) and different daily protein excretion (DPE): (DPE < 3.5 g; DPE > 3.5 g). RESULTS: Increased relative expression of hsa-miR-29-5p, hsa-miR-21-5p, and hsa-miR-196a-5p and decreased expression of hsa-miR-155-5p, hsa-miR-214-5p, hsa-miR-200a-5p, and hsa-miR-93-5p was demonstrated in urine of analyzed CKD patients. In subpopulation of chronic glomerulonephritis (CGN) patients, there was higher level of expression in urine of hsa-miR-155-5p, hsa-miR 214-3p, hsa-miR-93-5p, and hsa-miR-196a-5p in CGN with DPE < 3.5 g. CGN patients with eGFR < 60 ml/min showed higher expression level of miRNAs such as hsa-miR-214-3p, hsa-miR-29-5p, hsa-miR-93-5p, and hsa-miR-196-5p in urine. There was increase in hsa-miR 155-5p, hsa-miR-214-3p, and hsa-miR-200a-5p serum expression level in CKD population and reduction of hsa-miR-29a-5p, hsa-miR-21-5p, and hsa-miR-93-5p expression. Increased level of expression of hsa-miR-155-5p; hsa-miR-214-3p, hsa-miR-200a-5p, and hsa-miR-29-5p was found in CGN patients with eGFR > 60 ml/min. CONCLUSION: Increased relative expression of profibrogenic miRNAs in urine or serum of CKD patients with eGFR > 60 ml/min and DPE < 3.5 g may indicate higher degree of fibrosis at early CKD stages.

Relationship between CYP1B1 polymorphisms (c.142C > G, c.355G > T, c.1294C > G) and lung cancer risk in Polish smokers.

AIM: To determine whether three of CYP1B1 single nucleotide polymorphisms, c.142C > G, c.355G > T and c.1294C > G are associated with a lung cancer risk. PATIENTS & METHODS:  A total of 112 lung cancer patients and 100 controls were genotyped using the RFLP-PCR. RESULTS: In the c.142C > G polymorphisms, G allele was more frequent in lung cancer patients than in controls (p < 0.001), while in the c.1294C > G polymorphisms, C allele was more frequent in lung cancer patients, than in controls (p = 0.012). In the c.355G > T polymorphism, the distribution of alleles in both analyzed groups was similar. The GTC haplotype turned out to be correlated with the increased lung cancer risk, compared with the most common CGG haplotype (OR: 2.38; p = 0.001). CONCLUSION: CYP1B1 gene polymorphisms appear to influence lung cancer susceptibility.

New Candidate Genes for Lack of Sensitivity to Therapy in Pediatric Leukemias.

In the recent years, significant development of molecular genetics has contributed to the better understanding of leukemogenesis and classification of the different leukemia subtypes. Patients diagnosed with acute leukemia usually undergo chemotherapy, which involves the induction of remission, consolidation of remission and maintenance therapy. Patients are still vulnerable to relapse due to differences in the sensitivity of leukemia cells to the chemotherapeutic agent, because of the active drugs removal from the cells, improving the repair of DNA damage or abnormalities in the apoptotic pathway. Cell adhesion and miRNA expression level also affect the drug resistance. New candidate genes and genes correlated with the disease have been sought to increase the survival of patients with leukemia. Candidate gene is usually a loci located in a certain chromosomal region suspected of involvement to the disease course or its expression product regulates disease progression. There are classic and digital methods of finding candidate genes. These techniques are inexpensive, quick and easy to carry out. Unfortunately, due to insufficient knowledge of the disease etiology and low accuracy, researchers cannot detect all genes, involved in leukemogenesis and cell resistance. Currently, scientists have many tools used for selecting genes, such as expression microarrays, comparative genomic hybridization and next generation sequencing. Among the validation techniques for candidate genes, the mostly used ones are fluorescent in situ hybridization and real-time PCR. In our review we present 18 candidate genes of resistance to therapy in childhood leukemia.

Genomic and transcriptomic profiles and in vitro resistance to mitoxantrone and idarubicin in pediatric acute leukemias.

BACKGROUND: A major problem in the treatment of leukemia is the development of drug resistance to chemotherapeutic agents. METHODS: To determine the ex vivo drug resistance profile to anthracyclines, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) cytotoxicity assay was performed on mononuclear cells obtained from 155 patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). Gene expression profiles (for 51 patients with ALL and 16 with AML) were prepared on the basis of cRNA hybridization to oligonucleotide arrays of the human genome (Affymetrix). Hierarchical clustering, assignment location and biological function were investigated during the correlation analysis for identified probe sets. Comparative genomic hybridization (CGH) array profiles (34 patients with ALL and 12 with AML) were prepared on the basis of DNA hybridization to oligonucleotide arrays of the human genome (Agilent). The validation of the array results was performed by a quantitative reverse transcriptase polymerase chain reaction. RESULTS: The collected expression and CGH microarray experiment results indicate that the ITGB2, SCL6A7, CASP1 and DUSP genes may comprise a resistance marker for acute leukemia cells correlated with anthracyclines. Moreover, there were also identified chromosome rearrangements associated with drug resistance, such as del5q32-35.3 and amp8p12-p11.21. Precise genes, as well as genome aberrations, might be classified as targets in therapy. CONCLUSIONS: In AML, the resistance of blasts to idarubicin and mitoxantrone may reflect an impaired integrin pathway. In ALL, the development of resistance is caused by the inhibition of B and T cell activation. Copyright © 2016 John Wiley & Sons, Ltd.

An analysis of the expression of collagen I and III genes in the fascia of obese patients.

BACKGROUND: The etiology of incisional hernias in the population of morbidly obese patients remains unclear. Most likely, factors other than purely mechanical are at play; it has been ascertained that nonobese patients suffering from inguinal and incisional hernias display alterations in the architecture of the connective tissue. The goal of this study has been to evaluate and compare the relative expression of collagen type I and III genes in the rectus abdominis muscle sheath (RMS) of obese and nonobese individuals to investigate their possible influence on the quality of the connective tissue. MATERIALS AND METHODS: RMS specimens were harvested in the early stages of either bariatric or non-bariatric laparotomies; total RNA was isolated and enzymatically purified from the tissue samples. The resulting material was subjected to a quantitative and qualitative analysis; reverse transcription reactions were then performed and the resulting complementary DNA was used in real-time reverse transcription polymerase chain reactions. The biopsy specimens were also examined by scanning electron microscopy. RESULTS: The real-time reverse transcription polymerase chain reactions, performed on complementary DNA, provided specific amplicons for individual genes. The efficacy of the reactions was rather low. An almost twofold decrease of the relative expression level for type I and III collagen was observed between the two patient groups; the results did not reach statistical significance. Scanning electron microscope photographs have documented a marked difference in the ultrastructure of the RMS in both groups. CONCLUSIONS: The authors have shown that changes in messenger RNA levels for collagen type I and III genes may be related to the pathogenesis of incisional hernia through alterations in the ultrastructure of the RMS fascia. Our report should be considered preliminary; the results should be verified on a larger group of patients.

[Chorioangioma--a case study]. / Chorioangioma--opis przypadku.

Chorioangioma (chorionic angioma) is the most common non-malignant placental tumor Taking into account its morphological structure, it can have significant influence on fetal condition and pregnancy depending on its size. In the presented case a substantial placental tumor was diagnosed and complications typical for chorioangioma, such as fetal hemodynamic disorders, polyhydramnios, gestational diabetes and premature labor were observed. The applied treatment led to normalization of the fetal and maternal condition and to prolongation of the pregnancy

Array comparative genomic hybridization in pediatric acute leukemias.

Array comparative genomic hybridization has proven to be a very powerful tool in searching for new biomarkers which can find an application in clinical practise. CGH-array technology is satisfying in almost every possible way. It is highly specific, sensitive, simple, and relatively cheap. Thus, this modern method meets the demands of clinical application. An increasing knowledge about molecular pathways and pathologic genome alterations in acute leukemias enable to define unequivocal diagnosis, prognosis and to predict a response to individual compatible therapy. This review shows a various application of CGH-array in pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Analysis of relative expression level of VEGF ( vascular endothelial growth factor ), HIF-1α ( hypoxia inducible factor 1α ) and CTGF ( connective tissue growth factor ) genes in chronic glomerulonephritis (CGN) patients.

BACKGROUND/AIMS: Analysis of gene expression in renal tissue is considered to be a diagnostic tool predicting the clinical course of glomerulonephritis. The present study quantified the relative transcript levels of VEGF, CTGF and HIF-1α in renal tissue to establish their relationship with some clinical variables in patients suffering from chronic glomerulonephritis (CGN). METHODS: 28 patients (6F and 22M, mean age 51.2±15.0) with CGN were enrolled. Type of CNG recognized by kidney biopsy (histopatological evaluation) was as follows: minimal change disease (MCD)-3pts, IgA nephropathy-5pts, FSGS-3pts, membranous nephropathy-4pts, mesangio-proliferative glomerulonephritis-3pts; MPGN-1pts, lupus nephritis-6pts, granulomatosis with polyangitis-2 pts; hypertensive nephropathy- 3pts. Renal tissue from 3 individuals with normal eGFR and histology was taken as control. Mean clinical follow-up of patients was 12 months after biopsy eGFR and daily urinary protein excretion (DPE) was assessed at the time of biopsy and then in 6 months intervals. Real-time PCR was used to determine relative gene expression. The housekeeping gene GAPDH was used as normalization control. RESULTS: At the time of the biopsy relative expression of 3 analyzed genes was diminished in comparison to control. There were statistically significant differences in VEGF gene relative expression level in patients which varied according to eGFR and tendency in patients which varied according to DPE. HIF-alfa and CTGF gene showed only a tendency. CONCLUSIONS: Overexpression of the VEGF gene in subjects with DPE>3,5 g may point to insufficient oxygen supply in renal tissue which may result in tubulointerstitial fibrosis with further functional renal impairment and decline of eGFR.

Identification of the genes expression profile associated with the ex vivo resistance to etoposide in childhood acute leukemias.

INTRODUCTION: Drug resistance and the gene expression profiles might discriminate the therapy outcome, and indicate the subgroup of patients with poor prognosis. In this study we analyzed the gene expression profile in correlation with the profile of ex vivo resistance to etoposide in children with acute leukemias. METHODS: The ex vivo drug resistance profile was determined by the MTT cytotoxicity assay performed on leukemic blasts of 56 patients. Gene expression profiles were obtained from the results of hybridization of cRNA to Human Genome U133A 2.0 ologonucleotide arrays. The following analyses were performed: correlation analysis, hierarchical clustering, the assignment of location and function. Verification of data for four selected genes (MNDA, GH1, NUDT21, RHOG) was performed by quantitative real time polymerase chain reaction in the studied population and in an independent group of 54 leukemic patients. RESULTS: Using the permutation Spearman correlation test, a set of 233 probes/209 genes was selected. The global test confirmed the significance of the correlation of gene expression profile and resistance to etoposide (p<0.001). The NUDT21 (nudix, nucleoside diphosphate linked moiety X-type, motif 21) gene showed the strongest correlation with resistance to etoposide (FDR<0.0001%). CONCLUSIONS: Profiling of transcriptome may help in assessing the sensitivity to drugs used in chemotherapy. Resistance to etoposide is possibly associated with a change of expression of a large number of biologically important genes that influence several cellular mechanisms.

Expression profiles of signal transduction genes in ex vivo drug-resistant pediatric acute lymphoblastic leukemia.

AIM: Identification of signal transduction genes related to drug resistance in pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Ex vivo drug resistance in 107 children, divided into study and validation groups, was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) drug resistance assay. The gene expression profile was identified by microarray analysis and validated by quantitative reverse transcription polymerase chain reaction. RESULTS: A set of five genes involved in signal transduction, present in each resistance profile, was identified. The expression of four genes was up-regulated: Gardner-Rasheed feline sarcoma viral oncogene homolog, v-Fgr (FGR), S100 calcium binding protein A11 (S100A11), formyl peptide receptor 1 (FPR1), ArfGAP with RhoGAP domain, ankyrin repeat and PH1 domain (ARAP1), while the expression of growth hormone 1 (GH1) was found to be down-regulated in resistant leukemia blasts. CONCLUSION: Ex vivo exposure of leukemia cells to anticancer drugs induces changes in the expression of genes involved in cell signaling pathways. These genes play an important role in the mechanism of cellular drug resistance.

Gene expression signatures and ex vivo drug sensitivity profiles in children with acute lymphoblastic leukemia.

INTRODUCTION: Causes of treatment failure in acute lymphoblastic leukemia (ALL) are still poorly understood. Microarray technology gives new possibilities for the analysis of the biology of leukemias. We hypothesize that drug sensitivity in pediatric ALL is driven by specific molecular mechanisms that correlate with gene expression profiles assessed by microarray analysis. OBJECTIVE: The aim of the study was to determine the ex vivo resistance profiles of 20 antileukemic drugs and gene expression profiles, with relation to response to initial therapy. PATIENTS AND METHODS: Lymphoblasts were analyzed after bone marrow biopsy was obtained from 56 patients. The profile of in vitro resistance to drugs was determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) cytotoxicity assay. High-quality total RNA was prepared and hybridized to oligonucleotide arrays HG-U133A 2.0 Chip (Affymetrix). The expression of selected genes was tested by qualitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS AND CONCLUSIONS: The exposure of leukemic blasts to drugs initiates a complex cellular response, which reflects global changes in gene expression. Changes in the expression of several genes are highly correlated with drug resistance.

Sequencing technologies and genome sequencing.

The high-throughput - next generation sequencing (HT-NGS) technologies are currently the hottest topic in the field of human and animals genomics researches, which can produce over 100 times more data compared to the most sophisticated capillary sequencers based on the Sanger method. With the ongoing developments of high throughput sequencing machines and advancement of modern bioinformatics tools at unprecedented pace, the target goal of sequencing individual genomes of living organism at a cost of $1,000 each is seemed to be realistically feasible in the near future. In the relatively short time frame since 2005, the HT-NGS technologies are revolutionizing the human and animal genome researches by analysis of chromatin immunoprecipitation coupled to DNA microarray (ChIP-chip) or sequencing (ChIP-seq), RNA sequencing (RNA-seq), whole genome genotyping, genome wide structural variation, de novo assembling and re-assembling of genome, mutation detection and carrier screening, detection of inherited disorders and complex human diseases, DNA library preparation, paired ends and genomic captures, sequencing of mitochondrial genome and personal genomics. In this review, we addressed the important features of HT-NGS like, first generation DNA sequencers, birth of HT-NGS, second generation HT-NGS platforms, third generation HT-NGS platforms: including single molecule Heliscope™, SMRT™ and RNAP sequencers, Nanopore, Archon Genomics X PRIZE foundation, comparison of second and third HT-NGS platforms, applications, advances and future perspectives of sequencing technologies on human and animal genome research.

Relapse of acute lymphoblastic leukemia in children in the context of microarray analyses.

Over the last four decades the treatment of patients with newly diagnosed childhood acute lymphoblastic leukemia (ALL) has improved remarkably. However, still about 20% of children with ALL relapse despite risk-adapted polychemotherapy. The prognosis of relapsed ALL is relatively poor, even with modern aggressive chemotherapy. Identification of the biological and genetic mechanisms contributing to recurrence in patients with ALL is critical for the development of effective therapeutic strategies to treat refractory leukemic patients. Allogeneic hematopoietic stem-cell transplantation is the treatment of choice for many children with relapsed ALL. The gene expression profile obtained by microarray technology could provide important determinants of the drug response and clinical outcome in childhood ALL. Incorporation of the data on expression levels of newly identified genes into existing strategies of risk stratification might improve clinical management. Current microarray data show correlation of in vitro drug resistance with significant patterns of gene expression and explain clinical differences between early and late relapse. Genes involved in cell proliferation, self-renewal and differentiation, protein biosynthesis, carbohydrate metabolism, and DNA replication and repair are usually among those highly expressed in relapsed lymphoblasts. Current status and future perspectives of microarray data on gene expression and drug resistance profile in relapsed pediatric ALL are discussed in this review.

[Genetically-determined familial recurrent thanatophoric dysplasia]. / Rodzinnie uwarunkowana dysplazja tanatoforyczna.

Thanatophoric dysplasia was first described in 1967 by Maroteaux. It is one of the most common lethal neonatal dwarfisms. Estimated incidence of thanatophoric dysplasia is 0.2-0.5 per 10,000 births. In the following report we have described a prenatally diagnosed case of recurrent thanatophoric dysplasia in the same patient.

NOD2/CARD15 polymorphism in patients with rectal cancer.

BACKGROUND: Reports published in the past several years have not provided conclusive evidence regarding a relationship between the development of colorectal cancer and NOD2 gene mutations, though some geographic variability has been shown. MATERIAL/METHODS: The goal of the current project was to analyze the frequency of selected NOD2 gene variants, including P286S, R702W, G908R, and 1007fs, in the Polish population of patients with rectal cancer. Fifty-one rectal cancer patients undergoing treatment were included in the study. As a control group to provide a reference point for NOD2 polymorphism in the population, DNA obtained from cord blood collected from the placenta of 100 patients immediately after parturition was used. RESULTS: It was found that the aforementioned mutations were more frequent among the colorectal cancer patients and that the presence of the 1007fs variant might also be associated with young patient age. CONCLUSIONS: The analysis of the material does not allow presenting a conclusive answer as to whether the 1007fs, G908R, and R702W mutations or P268S polymorphism contribute to the development of sporadic colorectal cancer in the Polish population. Patients in some populations could likely benefit from instituting earlier colorectal cancer screening studies following the detection of the 1007fs mutation.

[Progress in the molecular classification of neoplasms in children]. / Postepy w kierunku molekularnej klasyfikacji nowotworów u dzieci.

Neoplasms are usually classified according to their histology, location, or the occurrence of specific molecular markers. The development of new technologies has led to the necessity of applying more efficient and universal methods of analysis, enabling a better diagnosis of the type of cancer and the determination of risk groups. Microarray technology constitutes the completion of conventional analytical methods. It shortens the time for a complete and precise characterization of cancer cells. Molecular classification based on microarray technology reflects the biological and clinical variety of neoplastic diseases. Gene expression profiles enable precise diagnosis, scoring and grading, and risk factor stratification. This technique might thus lead to targeted therapy in each type of cancer. This type of strategy has already been used in several types of pediatric cancer, such as leukemia, lymphoma, and sarcoma. In this review the possibilities of a microarray-based classification of pediatric cancers are presented.

[Gene expression profiles in acute lymphoblastic leukemia in children and adults]. / Profi le ekspresji genów w ostrej bialaczce limfoblastycznej u dzieci i doroslych.

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of white blood cell malignancies. Though a number of clinical and biological prognostic factors have been determined, the current patient stratification in this disease is still not satisfactory. Better knowledge and understanding of the biology of ALL is necessary for re-classification and risk-adapted therapy. Microarray technology, developed over last two decades, provides a potential for revolutionary changes in the diagnosis and monitoring of malignant diseases. Hundreds of genomic sequences can be analyzed in a single microarray experiment. A large amount of data have been obtained by microarray technology in hematological malignancies. Gene expression profiles based on this technology are currently being extensively studied in patients with ALL, and new data are being obtained in specific subgroups of patients. New markers based on gene expression might be identified and used to stratify patients and to individualize therapy. As the biology of ALL differs with respect to age, microarray technology can improve the determination of risk factors in each age group. This review presents the current status of knowledge on gene expression profiles in ALL in children and adults.