Transcription factors implicated in late megakaryopoiesis as markers of outcome after azacitidine and allogeneic stem cell transplantation in myelodysplastic syndrome

Giulia Falconi, Emiliano Fabiani, Marianna Criscuolo, Luana Fianchi, Carlo Finelli, Elisa Cerqui, Elvira Pelosi, Maria Screnci, Carmelo Gurnari, Ilaria Zangrilli, Massimiliano Postorino, Luca Laurenti, Alfonso Piciocchi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso

Research output: Contribution to journalArticle

Abstract

The hypomethylating agent azacitidine (AZA) is used to treat higher-risk myelodysplastic syndromes (HR-MDS) and elderly patients with low-blast count acute myeloid leukemia (LBC-AML). Platelet recovery is an early predictor of AZA response. We prospectively studied the expression profile of transcription factors, critical for late megakaryopoiesis and changes in their expression after AZA treatment in patients with HR-MDS and LBC-AML enrolled in the BMT-AZA trial (EudraCT number 2010-019673-15). Twenty-five additional patients with low-risk (LR)-MDS were also studied. At the time of diagnosis, GATA2 mRNA levels were significantly higher in MDS as compared to controls, with increasing levels from LR- to HR-MDS/AML. RUNX1 expression was also significantly higher in MDS, as compared to controls, but no differences were found between LR- and HR-MDS. Looking at biomarkers of response, we found that patients AZA responsive had higher basal GATA1 and lower FLI1 expression, compared to those with stable or progressive disease after treatment. Univariate analysis showed that increased GATA2 mRNA expression was associated with a worse overall survival. Our findings suggest that high GATA2 expression is a poor prognostic marker for survival in patients with HR-MDS and LBC-AML treated with azacitidine. Moreover, GATA1 and FLI1 mRNA expression may predict response to AZA treatment.

Original languageEnglish
Article number106191
JournalLeukemia Research
Volume84
DOIs
Publication statusPublished - Sep 1 2019

Fingerprint

Azacitidine
Myelodysplastic Syndromes
Stem Cell Transplantation
Transcription Factors
Acute Myeloid Leukemia
Messenger RNA
Survival
Therapeutics
Blood Platelets
Biomarkers

Keywords

  • Allogeneic stem cell transplantation
  • Azacitidine
  • Gene expression
  • Megakaryopoiesis
  • Myelodysplastic syndromes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Transcription factors implicated in late megakaryopoiesis as markers of outcome after azacitidine and allogeneic stem cell transplantation in myelodysplastic syndrome. / Falconi, Giulia; Fabiani, Emiliano; Criscuolo, Marianna; Fianchi, Luana; Finelli, Carlo; Cerqui, Elisa; Pelosi, Elvira; Screnci, Maria; Gurnari, Carmelo; Zangrilli, Ilaria; Postorino, Massimiliano; Laurenti, Luca; Piciocchi, Alfonso; Testa, Ugo; Lo-Coco, Francesco; Voso, Maria Teresa.

In: Leukemia Research, Vol. 84, 106191, 01.09.2019.

Research output: Contribution to journalArticle

Falconi, Giulia ; Fabiani, Emiliano ; Criscuolo, Marianna ; Fianchi, Luana ; Finelli, Carlo ; Cerqui, Elisa ; Pelosi, Elvira ; Screnci, Maria ; Gurnari, Carmelo ; Zangrilli, Ilaria ; Postorino, Massimiliano ; Laurenti, Luca ; Piciocchi, Alfonso ; Testa, Ugo ; Lo-Coco, Francesco ; Voso, Maria Teresa. / Transcription factors implicated in late megakaryopoiesis as markers of outcome after azacitidine and allogeneic stem cell transplantation in myelodysplastic syndrome. In: Leukemia Research. 2019 ; Vol. 84.
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AU - Falconi, Giulia

AU - Fabiani, Emiliano

AU - Criscuolo, Marianna

AU - Fianchi, Luana

AU - Finelli, Carlo

AU - Cerqui, Elisa

AU - Pelosi, Elvira

AU - Screnci, Maria

AU - Gurnari, Carmelo

AU - Zangrilli, Ilaria

AU - Postorino, Massimiliano

AU - Laurenti, Luca

AU - Piciocchi, Alfonso

AU - Testa, Ugo

AU - Lo-Coco, Francesco

AU - Voso, Maria Teresa

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N2 - The hypomethylating agent azacitidine (AZA) is used to treat higher-risk myelodysplastic syndromes (HR-MDS) and elderly patients with low-blast count acute myeloid leukemia (LBC-AML). Platelet recovery is an early predictor of AZA response. We prospectively studied the expression profile of transcription factors, critical for late megakaryopoiesis and changes in their expression after AZA treatment in patients with HR-MDS and LBC-AML enrolled in the BMT-AZA trial (EudraCT number 2010-019673-15). Twenty-five additional patients with low-risk (LR)-MDS were also studied. At the time of diagnosis, GATA2 mRNA levels were significantly higher in MDS as compared to controls, with increasing levels from LR- to HR-MDS/AML. RUNX1 expression was also significantly higher in MDS, as compared to controls, but no differences were found between LR- and HR-MDS. Looking at biomarkers of response, we found that patients AZA responsive had higher basal GATA1 and lower FLI1 expression, compared to those with stable or progressive disease after treatment. Univariate analysis showed that increased GATA2 mRNA expression was associated with a worse overall survival. Our findings suggest that high GATA2 expression is a poor prognostic marker for survival in patients with HR-MDS and LBC-AML treated with azacitidine. Moreover, GATA1 and FLI1 mRNA expression may predict response to AZA treatment.

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