Cargando…

Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia

Basophilia is a crucial prognostic variable in Ph-chromosome-positive chronic myeloid leukemia (CML). The ectoenzyme CD203c is an activation-linked surface antigen that is expressed specifically on basophil-committed progenitor cells and mature basophils. We examined the expression of CD203c on prog...

Descripción completa

Detalles Bibliográficos
Autores principales: Sadovnik, Irina, Ivanov, Daniel, Smiljkovic, Dubravka, Stefanzl, Gabriele, Degenfeld-Schonburg, Lina, Herndlhofer, Susanne, Eisenwort, Gregor, Hauswirth, Alexander W., Sliwa, Thamer, Keil, Felix, Sperr, Wolfgang R., Valent, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818308/
https://www.ncbi.nlm.nih.gov/pubmed/36611797
http://dx.doi.org/10.3390/cells12010003
_version_ 1784864953267650560
author Sadovnik, Irina
Ivanov, Daniel
Smiljkovic, Dubravka
Stefanzl, Gabriele
Degenfeld-Schonburg, Lina
Herndlhofer, Susanne
Eisenwort, Gregor
Hauswirth, Alexander W.
Sliwa, Thamer
Keil, Felix
Sperr, Wolfgang R.
Valent, Peter
author_facet Sadovnik, Irina
Ivanov, Daniel
Smiljkovic, Dubravka
Stefanzl, Gabriele
Degenfeld-Schonburg, Lina
Herndlhofer, Susanne
Eisenwort, Gregor
Hauswirth, Alexander W.
Sliwa, Thamer
Keil, Felix
Sperr, Wolfgang R.
Valent, Peter
author_sort Sadovnik, Irina
collection PubMed
description Basophilia is a crucial prognostic variable in Ph-chromosome-positive chronic myeloid leukemia (CML). The ectoenzyme CD203c is an activation-linked surface antigen that is expressed specifically on basophil-committed progenitor cells and mature basophils. We examined the expression of CD203c on progenitors and/or basophils in 21 healthy donors and 44 patients with CML. As expected, the numbers of CD203c(+) blood leukocytes were significantly higher in CML patients compared to controls (percentage of CD203c(+) cells among viable cells in CML at diagnosis: 4.19 ± 3.68% vs. controls: 0.53 ± 0.23%, p < 0.05). Moreover, CML basophils expressed higher levels of CD203c compared to normal basophils (median staining-index in CML at diagnosis: 29.41 ± 19.14 versus controls: 20.44 ± 13.45). We also found that the numbers and percentage of circulating CD203c(+) cells at diagnosis correlate with the disease-related risk-profile. Incubation of CML basophils with an anti-IgE-antibody resulted in further upregulation of CD203c. After successful treatment with imatinib and/or other BCR::ABL1 inhibitors leading to major or complete molecular responses, the numbers of CD203c(+) basophils decreased substantially in our CML patients compared to pre-treatment values. Together, CD203c is overexpressed on CML basophils, is further upregulated by IgE receptor cross-linking, and may serve as a biomarker to quantify basophilia in patients with CML at diagnosis and during therapy.
format Online
Article
Text
id pubmed-9818308
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98183082023-01-07 Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia Sadovnik, Irina Ivanov, Daniel Smiljkovic, Dubravka Stefanzl, Gabriele Degenfeld-Schonburg, Lina Herndlhofer, Susanne Eisenwort, Gregor Hauswirth, Alexander W. Sliwa, Thamer Keil, Felix Sperr, Wolfgang R. Valent, Peter Cells Article Basophilia is a crucial prognostic variable in Ph-chromosome-positive chronic myeloid leukemia (CML). The ectoenzyme CD203c is an activation-linked surface antigen that is expressed specifically on basophil-committed progenitor cells and mature basophils. We examined the expression of CD203c on progenitors and/or basophils in 21 healthy donors and 44 patients with CML. As expected, the numbers of CD203c(+) blood leukocytes were significantly higher in CML patients compared to controls (percentage of CD203c(+) cells among viable cells in CML at diagnosis: 4.19 ± 3.68% vs. controls: 0.53 ± 0.23%, p < 0.05). Moreover, CML basophils expressed higher levels of CD203c compared to normal basophils (median staining-index in CML at diagnosis: 29.41 ± 19.14 versus controls: 20.44 ± 13.45). We also found that the numbers and percentage of circulating CD203c(+) cells at diagnosis correlate with the disease-related risk-profile. Incubation of CML basophils with an anti-IgE-antibody resulted in further upregulation of CD203c. After successful treatment with imatinib and/or other BCR::ABL1 inhibitors leading to major or complete molecular responses, the numbers of CD203c(+) basophils decreased substantially in our CML patients compared to pre-treatment values. Together, CD203c is overexpressed on CML basophils, is further upregulated by IgE receptor cross-linking, and may serve as a biomarker to quantify basophilia in patients with CML at diagnosis and during therapy. MDPI 2022-12-20 /pmc/articles/PMC9818308/ /pubmed/36611797 http://dx.doi.org/10.3390/cells12010003 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sadovnik, Irina
Ivanov, Daniel
Smiljkovic, Dubravka
Stefanzl, Gabriele
Degenfeld-Schonburg, Lina
Herndlhofer, Susanne
Eisenwort, Gregor
Hauswirth, Alexander W.
Sliwa, Thamer
Keil, Felix
Sperr, Wolfgang R.
Valent, Peter
Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia
title Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia
title_full Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia
title_fullStr Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia
title_full_unstemmed Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia
title_short Identification of CD203c as a New Basophil-Specific Flow-Marker in Ph(+) Chronic Myeloid Leukemia
title_sort identification of cd203c as a new basophil-specific flow-marker in ph(+) chronic myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818308/
https://www.ncbi.nlm.nih.gov/pubmed/36611797
http://dx.doi.org/10.3390/cells12010003
work_keys_str_mv AT sadovnikirina identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT ivanovdaniel identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT smiljkovicdubravka identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT stefanzlgabriele identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT degenfeldschonburglina identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT herndlhofersusanne identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT eisenwortgregor identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT hauswirthalexanderw identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT sliwathamer identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT keilfelix identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT sperrwolfgangr identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia
AT valentpeter identificationofcd203casanewbasophilspecificflowmarkerinphchronicmyeloidleukemia