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Updated: May 13, 2026
06:39
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
A specific stem cell program and CD112 immunological axis dysfunctions underpinning monosomy 7-associated myeloid
Anair Graciela Lema Fernandez1, Carlotta Nardelli1, Martina Quintini1
1Institute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy.
Signal Transduction and Targeted Therapy
|May 11, 2026
Summary
Monosomy 7 in myeloid neoplasms disrupts immune checkpoints, leading to TIGIT/PVRIG receptor imbalance. Blocking these receptors enhances natural killer cell activity against cancer cells.
Area of Science:
- Hematology
- Molecular Biology
- Immunology
Background:
- Monosomy 7 is a poor prognostic factor in myeloid neoplasms.
- The molecular mechanisms underlying monosomy 7 are not fully understood.
- Chromosome 7 harbors genes critical for myeloid development and immune regulation.
Purpose of the Study:
- To elucidate the molecular landscape of monosomy 7 using an epi-transcriptomic approach.
- To identify novel therapeutic targets for myeloid neoplasms with monosomy 7.
- To investigate the role of the CD112 immune checkpoint axis in monosomy 7.
Main Methods:
- Epi-transcriptomic analysis to identify gene expression patterns.
- Immunohistochemistry to assess protein expression.
- Flow cytometry to analyze immune cell receptor expression.
- Ex vivo cytotoxicity assays with primary cells and autologous NK cells.
Main Results:
- Identified a novel 49-gene stemness program in monosomy 7, involving homeobox transcription factors and IKZF1/7p12.2 deficiency.
- Demonstrated CD112 upregulation on leukemic cells and altered TIGIT, PVRIG, and DNAM1 receptor expression on immune cells.
- Showed enhanced NK cell-mediated cytotoxicity against leukemic cells following TIGIT and PVRIG blockade.
Conclusions:
- Disclosed a dysfunctional TIGIT-PVRIG-DNAM1/CD112 axis in myeloid neoplasms with monosomy 7.
- Suggests targeting inhibitory immune receptors as a therapeutic strategy.
- Highlights the potential of exploiting autologous NK cell reactivity against this poor-prognosis cytogenetic abnormality.
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