Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine

High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to...

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Autores principales:	Carlo Pescia, Francesca Boggio, Giorgio Alberto Croci, Ramona Cassin, Marco Barella, Loredana Pettine, Gianluigi Reda, Elena Sabattini, Carlo Finelli, Umberto Gianelli
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	myelodysplastic syndromes azacitidine bone marrow histology Medicine R
Acceso en línea:	https://doaj.org/article/166e352b43c5476e9a09394aa0280788
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spelling	oai:doaj.org-article:166e352b43c5476e9a09394aa02807882021-11-11T17:29:13ZLymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine10.3390/jcm102148092077-0383https://doaj.org/article/166e352b43c5476e9a09394aa02807882021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/4809https://doaj.org/toc/2077-0383High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to identify any changes induced by azacitidine therapy or relevant correlations between therapy response and pre- or post-treatment features. Azacitidine treatment had no significant impact on bone marrow cellularity or morphological dysplastic features. On the contrary, although not statistically significant, we observed a slight decrease in CD34+ and CD117+ blasts and p53+ precursors after treatment. Moreover, pre-treatment IPSS-R cytogenetic score (<i>p</i> = 0.004), lymphocytic infiltrate (<i>p</i> = 0.017) and p53+ elements (<i>p</i> = 0.001) correlated with AML progression; pre-treatment lymphocytic infiltrate was also linked to better response to therapy (<i>p</i> = 0.004), suggesting an anti-tumoral role of bone marrow microenvironment. Post-treatment blast count impacted negatively on overall survival (<i>p</i> = 0.035) and risk of leukemic progression (<i>p</i> = 0.04), while both post-treatment lymphocytic infiltrate and p53+ elements showed significant correlation with treatment response (<i>p</i> = 0.004 and <i>p</i> = 0.003 respectively). Higher post-treatment p53+ elements correlated also with risk of leukemic progression (<i>p</i> = 0.013). Our results suggest the possible role of lymphocytic infiltrate and p53+ elements as predictive markers in MDS treated with azacitidine, disclosing new chapters in the understanding of MDS evolution and treatment.Carlo PesciaFrancesca BoggioGiorgio Alberto CrociRamona CassinMarco BarellaLoredana PettineGianluigi RedaElena SabattiniCarlo FinelliUmberto GianelliMDPI AGarticlemyelodysplastic syndromesazacitidinebone marrow histologyMedicineRENJournal of Clinical Medicine, Vol 10, Iss 4809, p 4809 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myelodysplastic syndromes azacitidine bone marrow histology Medicine R
spellingShingle	myelodysplastic syndromes azacitidine bone marrow histology Medicine R Carlo Pescia Francesca Boggio Giorgio Alberto Croci Ramona Cassin Marco Barella Loredana Pettine Gianluigi Reda Elena Sabattini Carlo Finelli Umberto Gianelli Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
description	High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to identify any changes induced by azacitidine therapy or relevant correlations between therapy response and pre- or post-treatment features. Azacitidine treatment had no significant impact on bone marrow cellularity or morphological dysplastic features. On the contrary, although not statistically significant, we observed a slight decrease in CD34+ and CD117+ blasts and p53+ precursors after treatment. Moreover, pre-treatment IPSS-R cytogenetic score (<i>p</i> = 0.004), lymphocytic infiltrate (<i>p</i> = 0.017) and p53+ elements (<i>p</i> = 0.001) correlated with AML progression; pre-treatment lymphocytic infiltrate was also linked to better response to therapy (<i>p</i> = 0.004), suggesting an anti-tumoral role of bone marrow microenvironment. Post-treatment blast count impacted negatively on overall survival (<i>p</i> = 0.035) and risk of leukemic progression (<i>p</i> = 0.04), while both post-treatment lymphocytic infiltrate and p53+ elements showed significant correlation with treatment response (<i>p</i> = 0.004 and <i>p</i> = 0.003 respectively). Higher post-treatment p53+ elements correlated also with risk of leukemic progression (<i>p</i> = 0.013). Our results suggest the possible role of lymphocytic infiltrate and p53+ elements as predictive markers in MDS treated with azacitidine, disclosing new chapters in the understanding of MDS evolution and treatment.
format	article
author	Carlo Pescia Francesca Boggio Giorgio Alberto Croci Ramona Cassin Marco Barella Loredana Pettine Gianluigi Reda Elena Sabattini Carlo Finelli Umberto Gianelli
author_facet	Carlo Pescia Francesca Boggio Giorgio Alberto Croci Ramona Cassin Marco Barella Loredana Pettine Gianluigi Reda Elena Sabattini Carlo Finelli Umberto Gianelli
author_sort	Carlo Pescia
title	Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
title_short	Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
title_full	Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
title_fullStr	Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
title_full_unstemmed	Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
title_sort	lymphocytic infiltrate and p53 protein expression as predictive markers of response and outcome in myelodysplastic syndromes treated with azacitidine
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/166e352b43c5476e9a09394aa0280788
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Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine

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