High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia

J Exp Clin Cancer Res. 2016 Apr 5;35:64. doi: 10.1186/s13046-016-0333-z.

Abstract

Background: B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30% lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61% of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients.

Methods: We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT).

Results: We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome.

Conclusions: Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.

Keywords: Acute lymphoblastic leukemia; Complete remission; Gene expression profile; Minimal residual disease; Translational research.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Hispanic Americans / genetics*
  • Humans
  • Immunoglobulin J-Chains / genetics*
  • Inhibitor of Differentiation Protein 1 / genetics*
  • Inhibitor of Differentiation Proteins / genetics*
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis / methods
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / ethnology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome
  • Up-Regulation*
  • Young Adult

Substances

  • ID1 protein, human
  • Immunoglobulin J-Chains
  • Inhibitor of Differentiation Protein 1
  • Inhibitor of Differentiation Proteins
  • Neoplasm Proteins
  • ID3 protein, human