Investigating novel prognostic factors in patients with acute myeloid leukemia: absolute lymphocyte count and immune transcriptomic bone marrow profile.

Cristiano, Gianluca (2025) Investigating novel prognostic factors in patients with acute myeloid leukemia: absolute lymphocyte count and immune transcriptomic bone marrow profile., [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia, ematologia e patologia, 37 Ciclo. DOI 10.48676/unibo/amsdottorato/12028.
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Abstract

Concurrently to the extensive characterization of AML blast cell, in recent years the study and interest of microenvironment (ME) in bone marrow (BM) in which AML cells form and grow up and the immunological network established has been rapidly raising. Absolute lymphocyte count (ALC) is known to be an independent prognostic factor for overall survival (OS) in patients with lymphomas and solid cancers. In AML patients, enhanced ALC recovery after intensive chemotherapy (IC) has been associated with superior OS. Our project explores the immune transcriptomic profile variation in AML patients treated with chemotherapy and, concurrently, the impact of a clinical prognostic parameter as ALC. Firstly, we performed a Pancancer Human NanoString panel, using BM samples collected from 48 AML patients, to describe distribution expression before and after therapy. Of note, Nanostring analysis showed significant differences in transcriptomic immune environment between onset and post therapy, especially in gene belonging to immune response. Secondly, we investigated ALC recovery in the total 188 patients population, from Bologna Seràgnoli Hematology Institute, who were responsive to IC. Among patients treated with “3+7-based” regimen (51,6%), a relevant correlation with OS of patients with ≥500/mm3 ALC (31,9%) vs those under the cut-off (19,6%) was observed at ALC-15. This finding was further statistically significant in patients with ALC≥500/mm3 in all 4 TPs (p=0.02). ALC recovery was also correlated with MRD value. Among “3+7-based” patients who obtained MRD negativity (n = 52), those who had ≥500/mm3ALC in all ALC TPs (n=29) and in ALC-15 (n=35) resulted in a globally better OS as compared to patients with <500/mm3 ALC. ALC may represent a predictive biomarker to identify patients who may benefit from HSCT. A difference can be spotted when comparing BM onset samples analyzed with NanoString panel, according to ALC and MRD, but more extensive subanalysis are required.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Cristiano, Gianluca
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
37
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
absolute lymphocyte count; acute myeloid leukemia; immune microenvironment; allogeneic transplantation; minimal residual disease.
DOI
10.48676/unibo/amsdottorato/12028
Data di discussione
8 Aprile 2025
URI

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