Role of Par-4 in B-cell hematological malignancies

Sunil K. Noothi, Mary K. McKenna, Sara S. Alhakeem, James P. Collard, J. T. Greene, Natarajan Muthusamy, Vivek M. Rangnekar, Subbarao Bondada

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Prostate apoptosis response-4 (Par-4) was identified as a tumor suppressor protein that is silenced by promoter methylation in various cancers and has been shown to induce apoptosis selectively in cancer cells but not in normal cells. Par-4 interacts with a variety of partners in cells to mediate various cellular responses and appears to have a pro-apoptotic role in non-hematological tumors. Here, we summarize the literature on the role of Par-4 in hematological cells that is in contrast to its classic pro-apoptotic role. Par-4 is expressed basally in various hematopoietic cells and malignancies at the mRNA and protein level, but is predominant in the early stages of B-cell maturation and specifically in chronic lymphocytic leukemia (CLL). CLL B cells express higher levels of Par-4 than normal B-cell subsets and constitutively active B-cell receptor signaling (BCR) maintains high Par-4 levels in these cells, suggesting a novel regulation of Par-4 through BCR signaling. CLL cell growth is dependent on BCR signaling-mediated Par-4 expression, which is in part due to downregulation of p21 by Par-4. Bcl2 and NF-κB pathways cause differential regulation of apoptotic genes in contrast to non-hematological cancers, and Par-4 may also play a significant role in tumor microenvironment. Thus, Par-4 appears to have unique roles in hematological malignancies.

Original languageEnglish
Title of host publicationTumor Suppressor Par-4
Subtitle of host publicationRole in Cancer and Other Diseases
Number of pages16
ISBN (Electronic)9783030805586
StatePublished - Jan 1 2022

Bibliographical note

Publisher Copyright:
© Springer Nature Switzerland AG 2021. All rights reserved.


  • B cells
  • B-cell receptor
  • Chronic lymphocytic leukemia
  • Lymphoma
  • Microenvironment
  • p21
  • Par-4
  • Splenectomy
  • Stromal cells
  • Tcl1

ASJC Scopus subject areas

  • Medicine (all)


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