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

Genes Chromosomes Cancer. 2019 Nov;58(11):815-819. doi: 10.1002/gcc.22788. Epub 2019 Aug 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Disease Progression
  • Female
  • Gene Deletion
  • Humans
  • Ikaros Transcription Factor / genetics*
  • Ikaros Transcription Factor / metabolism
  • Male
  • Neoplasm, Residual
  • Philadelphia Chromosome
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Prognosis
  • Recurrence

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • IKZF1 protein, human
  • Ikaros Transcription Factor