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

Szczepanek, Joanna; Jarząb, Michał; Oczko‐Wojciechowska, Małgorzata; Kowalska, M.; Tretyn, Andrzej; Haus, Olga; Pogorzała, Monika; Wysocki, Mariusz; Jarząb, Barbara; Styczyński, Jan

doi:10.1007/s13353-011-0073-x

Cited by 10 publications

(9 citation statements)

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“…Determining the type (ALL or AML) and subtype of the leukemia is performed by testing samples of the blood, bone marrow, and sometimes lymph nodes or cerebrospinal fluid[ 23 ]. In recent years, there has been significant progress in the use of comprehensive transcriptomic and genomic methods (expression, single nucleotide polymorphism, and comparative genomic hybridization arrays; whole exome, whole transcriptome, and whole genome sequencing) to identify leukemia subtypes and inherited and somatic genomic changes, but nevertheless, much work is needed to define the intrinsic and extrinsic determinants of leukemia progression, prognosis, and drug response[ 8 , 38 , 39 ]. A summary of miRNA marker functions, based on the example of pediatric ALL, is presented in Table 1 .…”

Section: Role Of Microrna In Diagnosis and Classificationmentioning

confidence: 99%

Role of microRNA dysregulation in childhood acute leukemias: diagnostics, monitoring and therapeutics: A comprehensive review

Szczepanek

2020

WJCO

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MicroRNAs (miRNAs) are short noncoding RNAs that regulate the expression of genes by sequence-specific binding to mRNA to either promote or block its translation; they can also act as tumor suppressors ( e.g ., let-7b, miR-29a, miR-99, mir-100, miR-155, and miR-181) and/or oncogenes ( e.g ., miR-29a, miR-125b, miR-143-p3, mir-155, miR-181, miR-183, miR-196b, and miR-223) in childhood acute leukemia (AL). Differentially expressed miRNAs are important factors associated with the initiation and progression of AL. As shown in many studies, they can be used as noninvasive diagnostic and prognostic biomarkers, which are useful in monitoring early stages of AL development or during therapy ( e.g ., miR-125b, miR-146b, miR-181c, and miR-4786), accurate classification of different cellular or molecular AL subgroups ( e.g ., let-7b, miR-98, miR-100, miR-128b, and miR-223), and identification and development of new therapeutic agents ( e.g ., mir-10, miR-125b, miR-203, miR-210, miR-335). Specific miRNA patterns have also been described for commonly used AL therapy drugs ( e.g ., miR-125b and miR-223 for doxorubicin, miR-335 and miR-1208 for prednisolone, and miR-203 for imatinib), uncovering miRNAs that are associated with treatment response. In the current review, the role of miRNAs in the development, progression, and therapy monitoring of pediatric ALs will be presented and discussed.

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Section: Role Of Microrna In Diagnosis and Classificationmentioning

confidence: 99%

Role of microRNA dysregulation in childhood acute leukemias: diagnostics, monitoring and therapeutics: A comprehensive review

Szczepanek

2020

WJCO

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“…In this work, the sensibility to PIP4K2A inhibition was modulated by CDKN1A (p21) and mTOR activation. Szczepanek and colleagues (Szczepanek, et al, 2012), using ex vivo drug sensitivity experiments and DNA microarray analysis in childhood acute lymphoblastic leukemia PIP4K2A (phosphatidylinositol-5-phosphate 4-kinase, type II, alpha) Lima K, Machado-Neto JA Atlas Genet Cytogenet Oncol Haematol. 2016;20(7) cells, found that PIP4K2A gene signature was associated with drug resistance for vincristine, thioguanine, melphalan and doxorubicin.…”

Section: Acute Leukemiamentioning

confidence: 99%

PIP4K2A (phosphatidylinositol-5-phosphate 4-kinase, type II, alpha)

Lima¹,

Machado-Neto²

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…Research focusing on the simultaneous examination of thousands of cancer cell genes has been ongoing for many years. The objective of such analyses is the selection of genes associated with cancer's developmental course, as well as that associated with sensitivity or resistance of cancer cells to drugs [39][40][41]. One of the most important directions for current cancer research is to explore the processes that enable multi-drug resistance to develop; in doing so, we hope to find ways to avoid or prevent those processes from occurring, and to discover new and effective resistance gene inhibitors.…”

Section: Resistance To Therapymentioning

confidence: 99%

Pediatric acute myeloid leukemia and drug resistance in the context of microarray studies

2015

Adv Pediatr Res

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Genome and transcriptome profiling methods are increasingly used in studies of pediatric acute myeloid leukemia (AML). AML can be distinguished from acute lymphoblastic leukemia (ALL) on the basis of gene expression profiles; so too can the various subclasses of these two forms be further distinguished and genetically characterized. Genome-wide analysis studies (GWAS) have also contributed to new insights into the biological basis of the mechanisms of drug resistance, and allow the identification of new prognostic factors and the potential for targeted therapy. On the basis of changes in gene expression level, it is also possible to predict the risk of early recurrence and prognosis at the time of diagnosis of de novo leukemia. Although the possibility to analyze gene expression profiles already presents significant progress in our understanding of the complex pathobiology of pediatric AML, the introduction of new microarrays formats, such as CGH, SNP, CpG islands or antibodies, should be considered to build a complete picture of the cells in this form of cancer.

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

Abstract: 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.

Cited by 10 publications

References 44 publications

Role of microRNA dysregulation in childhood acute leukemias: diagnostics, monitoring and therapeutics: A comprehensive review

Role of microRNA dysregulation in childhood acute leukemias: diagnostics, monitoring and therapeutics: A comprehensive review

PIP4K2A (phosphatidylinositol-5-phosphate 4-kinase, type II, alpha)

Pediatric acute myeloid leukemia and drug resistance in the context of microarray studies

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