Targeting chronic myeloid leukemia stem/progenitor cells using venetoclax-loaded immunoliposome

Mohammad Houshmand, Francesca Garello, Rachele Stefania, Valentina Gaidano, Alessandro Cignetti, Michela Spinelli, Carmen Fava, Mahin Nikougoftar Zarif, Sara Galimberti, Ester Pungolino, Mario Annunziata, Luigia Luciano, Giorgina Specchia, Monica Bocchia, Gianni Binotto, Massimiliano Bonifacio, Bruno Martino, Patrizia Pregno, Fabio Stagno, Alessandra IurloSabina Russo, Silvio Aime, Paola Circosta, Giuseppe Saglio

Research output: Contribution to journalArticlepeer-review

Abstract

CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster re-gion/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolu-tionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are de-tectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.

Original languageEnglish
Article number1311
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number6
DOIs
Publication statusPublished - Mar 2 2021

Keywords

  • CD26
  • Chronic myeloid leukemia
  • Immunoliposome
  • Leukemia stem cell
  • Liposome
  • Nanomedicine
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Targeting chronic myeloid leukemia stem/progenitor cells using venetoclax-loaded immunoliposome'. Together they form a unique fingerprint.

Cite this