Oncotarget

Research Papers:

Genomic loss of HLA alleles may affect the clinical outcome in low-risk myelodysplastic syndrome patients

Paola Montes, Martin Kerick, Mónica Bernal _, Francisca Hernández, Pilar Jiménez, Pilar Garrido, Ana Márquez, Manuel Jurado, Javier Martin, Federico Garrido and Francisco Ruiz-Cabello

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Oncotarget. 2018; 9:36929-36944. https://doi.org/10.18632/oncotarget.26405

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Abstract

Paola Montes1,*, Martin Kerick2,*, Mónica Bernal1, Francisca Hernández3, Pilar Jiménez1, Pilar Garrido3, Ana Márquez2, Manuel Jurado3, Javier Martin2, Federico Garrido1,4,5 and Francisco Ruiz-Cabello1,4,5

1Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Granada, Spain

2Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, Spain

3UGC de Hematología, Hospital Universitario Virgen de las Nieves, Granada, Spain

4Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain

5Departamento Bioquímica, Biología Molecular e Inmunología III, Universidad de Granada, Granada, Spain

*These authors have contributed equally to this work

Correspondence to:

Mónica Bernal, email: [email protected]

Keywords: human leukocyte antigen (HLA); loss of heterozygosity (LOH); single nucleotide polymorphism array (SNP array); myelodysplastic syndrome (MDS); hematopoietic stem cell transplantation (HSCT)

Received: August 22, 2018     Accepted: October 24, 2018     Published: December 11, 2018

ABSTRACT

The Revised International Prognostic Score and some somatic mutations in myelodysplastic syndrome (MDS) are independently associated with transformation to acute myeloid leukemia (AML). Immunity has also been implicated in the pathogenesis of MDS, although the underlying mechanism remains unclear. We performed a SNP array on chromosome 6 in CD34+ purified blasts from 19 patients diagnosed with advanced MDS and 8 patients with other myeloid malignancies to evaluate the presence of loss of heterozygosity (LOH) in HLA and its impact on disease progression. Three patients had acquired copy-neutral LOH (CN-LOH) on 6p arms, which may disrupt antigen presentation and act as a mechanism for immune system evasion. Interestingly, these patients had previously been classified at low risk of AML progression, and the poor outcome cannot be explained by the acquisition of adverse mutations. LOH HLA was not detected in the remaining 24 patients, who all had adverse risk factors. In summary, the clinical outcome of patients with advanced MDS might be influenced by HLA allelic loss, wich allows subclonal expansions to evade cytotoxic-T and NK cell attack. CN-LOH HLA may therefore be a factor favoring MDS progression to AML independently of the somatic tumor mutation load.


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