Elevated expression of pleiotrophin in lymphocytic leukemia CD19+ B cells

APMIS. 2014 Oct;122(10):905-13. doi: 10.1111/apm.12229. Epub 2014 Apr 3.

Abstract

Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal tissues, but seldom in healthy adult tissues. While PTN has been reported to be expressed in many types of tumors as well as at high serum concentrations in patients with many types of cancer, to date, there has been no report that PTN is expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+) subset of B cells from peripheral blood from healthy adults, B-cell acute lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-CLL) patients and examined these cells for PTN mRNA and protein expression. We used immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL patients, but barely expressed in B cells from healthy adults. We also examined PTN expression at the nucleic acid level using reverse transcription polymerase chain reaction (RT-PCR) and northern blotting and detected a high levels of PTN transcripts in the CD19(+) B cells from both groups of leukemia patients, but very few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity of the PTN transcripts correlated with the severity of disease. Moreover, suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN antibody suggests that PTN may be a new target for the treatment of lymphocytic leukemia.

Keywords: B-cell chronic lymphocytic leukemia; Cluster of differentiation 19 positive B cells; acute B lymphoblastic leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD19 / genetics*
  • Antigens, CD19 / immunology*
  • Apoptosis / genetics
  • Apoptosis / immunology
  • B-Lymphocytes / immunology*
  • Carrier Proteins / genetics*
  • Carrier Proteins / immunology*
  • Case-Control Studies
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Cytokines / genetics*
  • Cytokines / immunology*
  • Female
  • Humans
  • Leukemia, Lymphoid / genetics*
  • Leukemia, Lymphoid / immunology*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Young Adult

Substances

  • Antigens, CD19
  • Carrier Proteins
  • Cytokines
  • RNA, Messenger
  • pleiotrophin