Last update 01 Nov 2024

PARP x ABL1

Last update 01 Nov 2024

Basic Info

Related Targets

PARPABL1

Drugs associated with PARP x ABL1

AMXI-3001

Target

ABL1 x PARP

Mechanism

ABL1 inhibitors [+1]

Active Org.

Atlasmedx, Inc.

Originator Org.

Atlasmedx, Inc.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PARP x ABL1

100 Translational Medicine associated with PARP x ABL1

0 Patents (Medical) associated with PARP x ABL1

Literatures (Medical) associated with PARP x ABL1

01 Sep 2024·Cancer Diagnosis & Prognosis

Association of PARP1 Expression Levels and Clinical Parameters in Different Leukemic Subtypes With BCR::ABL1 p190+ Translocation

Article

Author: DE Pinho Pessoa, Flávia Melo Cunha ; Ribeiro, Rodrigo Monteiro ; DA Silva, Jean Breno Silveira ; SEABRA, ALINE DAMASCENO ; DE Sousa Oliveira, Deivide ; Dias Nogueira, Beatriz Maria ; DE Moraes Filho, Manoel Odorico ; Burbano, Rommel Rodriguez ; DE MORAIS, GUILHERME PASSOS ; MELLO JÚNIOR, FERNANDO AUGUSTO RODRIGUES ; Moreira-Nunes, Caroline Aquino ; Seabra, Aline Damasceno ; BURBANO, ROMMEL RODRIGUEZ ; DE MORAES FILHO, MANOEL ODORICO ; DE PINHO PESSOA, FLÁVIA MELO CUNHA ; DE Moraes, Maria Elisabete Amaral ; Mello Júnior, Fernando Augusto Rodrigues ; Machado, Caio Bezerra ; MOREIRA-NUNES, CAROLINE AQUINO ; Khayat, André Salim ; DA SILVA, JEAN BRENO SILVEIRA ; DIAS NOGUEIRA, BEATRIZ MARIA ; MACHADO, CAIO BEZERRA ; RIBEIRO, RODRIGO MONTEIRO ; DE Morais, Guilherme Passos ; DE SOUSA OLIVEIRA, DEIVIDE ; KHAYAT, ANDRÉ SALIM ; DE MORAES, MARIA ELISABETE AMARAL

Background/Aim: Although the reciprocal translocation t(9;22)(q34;q11) is a hallmark of chronic myeloid leukemia (CML), it is also present in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Depending on the gene's breakpoint, it is possible to obtain three isoforms, among which p190 stands out for the poor prognosis it induces whenever it appears. Due to the genomic instability induced by BCR::ABL1, it is proposed to expand the applicability of poly-ADP-ribose polymerase-1 (PARP1) and its inhibitors in hematological neoplasms. Materials and Methods: We measured the expression levels of PARP1 by quantitative real-time PCR (qPCR) using TaqMan®, correlating its expression with BCR::ABL1 p190+, to evaluate its influence in the clinic of adult patients. Results: We found that PARP1 is expressed differently in ALL, AML and CML and that p190 transcripts do not follow a linear pattern in these populations. We also found that PARP1 expression is not correlated with age, white blood cell and the amount of p190 transcripts. Conclusion: Despite the lack of statistical correlation between the variables analyzed, the role of PARP1 in BCR::ABL1 leukemia cannot be ruled out, given the instability profile promoted by this translocation. Finally, further studies involving a larger sample of patients are needed, as well as investigations into other molecular pathways that may impact on the pathogenesis of different BCR::ABL1 leukemic subtypes.

28 Jun 2024·Bioinformatics

Representing mutations for predicting cancer drug response

Article

Author: Wall, Patrick ; Ideker, Trey

AbstractMotivationPredicting cancer drug response requires a comprehensive assessment of many mutations present across a tumor genome. While current drug response models generally use a binary mutated/unmutated indicator for each gene, not all mutations in a gene are equivalent.ResultsHere, we construct and evaluate a series of predictive models based on leading methods for quantitative mutation scoring. Such methods include VEST4 and CADD, which score the impact of a mutation on gene function, and CHASMplus, which scores the likelihood a mutation drives cancer. The resulting predictive models capture cellular responses to dabrafenib, which targets BRAF-V600 mutations, whereas models based on binary mutation status do not. Performance improvements generalize to other drugs, extending genetic indications for PIK3CA, ERBB2, EGFR, PARP1, and ABL1 inhibitors. Introducing quantitative mutation features in drug response models increases performance and mechanistic understanding.Availability and implementationCode and example datasets are available at https://github.com/pgwall/qms.

01 Jan 2024·Blood Cells, Molecules, and Diseases

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells

Article

Author: de Miranda, Lívia Bassani Lins ; Carlos, Jorge Antonio Elias Godoy ; Parducci, Natália Sudan ; Rego, Eduardo Magalhães ; Traina, Fabiola ; Machado-Neto, João Agostinho ; de Almeida, Bruna Oliveira ; Fonseca, Natasha Peixoto ; Lima, Keli ; Garnique, Anali Del Milagro Bernabe

Myeloproliferative neoplasms (MPN) are consolidated as a relevant group of diseases derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid lineage. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the CSF3R gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2^V617F increased the expression of the aurora kinase A (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCR::ABL1 and JAK2^V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3R^T618I-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R^T618I mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, clonogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced histone H3 phosphorylation, aurora A inhibitor I and reversine reduced STAT5 phosphorylation, and AZD1152-HQPA and reversine induced PARP1 cleavage and γH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.

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