New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

Moorman, Anthony V.

doi:10.3324/haematol.2015.141101

Cited by 176 publications

(188 citation statements)

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“…Poor genetic and molecular profiles are more prevalent in adults than in children, 1 and molecular abnormalities in genes associated with B-cell development (ie, IKZF1), cell cycle (ie, CDKN2A/B), and epigenetic regulators (ie, CREBBP) play relevant roles in disease progression. Genetic factors are critical for predicting patient outcome and are increasingly being considered to assign adapted or targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Ribera

Zamora

Vives

et al. 2019

Genes Chromosomes & Cancer

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Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high‐risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome‐negative B‐cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD‐negative after induction therapy.

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Section: Introductionmentioning

confidence: 99%

Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Ribera

Zamora

Vives

et al. 2019

Genes Chromosomes & Cancer

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“…In 19 BCP-ALL patients without an established abnormality (B-other) 29 or targetable kinase-activating lesions, 3 fluorescence in situ hybridization was performed (probes from Cytocell, Cambridge, United Kingdom). Detailed protocols are provided in the supplemental Data (available on the Blood Web site).…”

Section: Genomic Characterization Of Leukemia Samplesmentioning

confidence: 99%

Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

Frismantas

Dobay

Rinaldi

et al. 2017

Blood

191

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“…The side contribution of the partner genes in cell transformation has been demonstrated in several cases of chimeric genes. Multiple partner genes in fusions contribute functionally to the activity of the known oncogene like MYC, MLL, RARA, ALK and RUNX1 . Most of the genes fused to CCDC6, identified so far, are well known oncogenes that promotes the enhancement of cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

CCDC6: the identity of a protein known to be partner in fusion

Cerrato

Merolla

Morra

et al. 2017

Intl Journal of Cancer

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Coiled Coil Domain Containing 6 gene, CCDC6, was initially isolated as part of a tumorigenic DNA originated by the fusion of CCDC6 with the tyrosine kinase of RET receptor, following a paracentric inversion of chromosome 10. For a long time, CCDC6 has been considered as an accidental partner of the RET protooncogene, providing the promoter and the first 101 aa necessary for the constitutive activation of the oncogenic Tyrosine Kinase (TK) RET in thyroid cells. With the advent of more refined diagnostic tools and bioinformatic algorithms, an exponential growth in fusion genes discoveries has allowed the identification of CCDC6 as partner of genes other than RET in different tumor types. CCDC6 gene product has a proper role in sustaining the DNA damage checkpoints in response to DNA damage. The inactivation of CCDC6 secondary to chromosomal rearrangements or gene mutations could enhance tumor progression by impairing the apoptotic response upon the DNA damage exposure, contributing to the generation of radio- and chemoresistance. Preclinical studies indicate that the attenuation of CCDC6 in cancer, while conferring a resistance to cisplatinum, sensitizes the cancer cells to the small molecule inhibitors of Poly (ADP-ribose) polymerase (PARP1/2) with a synthetic lethal effect. Several CCDC6 mutations and gene rearrangements have been described so far in different types of cancer and CCDC6 may represent a possible predictive biomarker of tumor resistance to the conventional anticancer treatments. Nevertheless, the detection of a CCDC6 impairment in cancer patients may help to select, in future clinical trials, those patients who could benefit of PARP-inhibitors treatment alone or in combination with other treatments.

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New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

Cited by 176 publications

References 100 publications

Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

CCDC6: the identity of a protein known to be partner in fusion

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