Acute myeloid leukemia (AML) comprises a genetically and clinically heterogeneous group of aggressive haematological neoplasms, characterized by clonal proliferation, reduced maturation of malignant myeloid precursors and resistance to apoptosis. The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death, and it can be over overexpressed in AML, but is uncertain if its overexpression could have a prognostic impact. We perform immunophenotypic analysis to identify blast cells population from bone marrow samples of all newly diagnosed AML patients in our haematology unit. At data cut off, we enrol 68 newly diagnosed AML pts from December 2019 to January 2023. 36 male 32 female, the median age 68.5ys (range 20-92ys), 42/68 were treated with intensive chemotherapy, 26/68 were treated with hypomethylating agents or low dose cytarabine. We studied the prognostic biologic futures of the AML samples, especially NPM1, FLT3 mutations and karyotype. The expression of BCL2 is classified by using as a parameter the MFI, mean fluorescence intensity, obtained by calculating the ratio between the median intensity of BCL2 in the sample and the corresponding isotipic control. After several statistical analysis we couldn’t prove a prognostic impact of the over expression of BCL2 about OS, as some papers had shown before. We tried to find also a statistical correlation between over expression of BCL2 and other biological futures with prognostic role, but neither mutations of NPM1, FLT3 were related to the expression of BCL2. Finally we study OS of our cohort of patients treated with intensive chemotherapy and low dose therapies and we found a very good prognosis for responder patients treated with intensive chemotherapy with a median OS not reached after 2 years of follow up. Unfortunately the prognosis of older patients, event with the introduction of new target therapies remain poor, with a median OS less then one year.

New prognostic markers in acute myeloid lekemia: focus on BCL2 expression

CIOFINI, SARA
2023

Abstract

Acute myeloid leukemia (AML) comprises a genetically and clinically heterogeneous group of aggressive haematological neoplasms, characterized by clonal proliferation, reduced maturation of malignant myeloid precursors and resistance to apoptosis. The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death, and it can be over overexpressed in AML, but is uncertain if its overexpression could have a prognostic impact. We perform immunophenotypic analysis to identify blast cells population from bone marrow samples of all newly diagnosed AML patients in our haematology unit. At data cut off, we enrol 68 newly diagnosed AML pts from December 2019 to January 2023. 36 male 32 female, the median age 68.5ys (range 20-92ys), 42/68 were treated with intensive chemotherapy, 26/68 were treated with hypomethylating agents or low dose cytarabine. We studied the prognostic biologic futures of the AML samples, especially NPM1, FLT3 mutations and karyotype. The expression of BCL2 is classified by using as a parameter the MFI, mean fluorescence intensity, obtained by calculating the ratio between the median intensity of BCL2 in the sample and the corresponding isotipic control. After several statistical analysis we couldn’t prove a prognostic impact of the over expression of BCL2 about OS, as some papers had shown before. We tried to find also a statistical correlation between over expression of BCL2 and other biological futures with prognostic role, but neither mutations of NPM1, FLT3 were related to the expression of BCL2. Finally we study OS of our cohort of patients treated with intensive chemotherapy and low dose therapies and we found a very good prognosis for responder patients treated with intensive chemotherapy with a median OS not reached after 2 years of follow up. Unfortunately the prognosis of older patients, event with the introduction of new target therapies remain poor, with a median OS less then one year.
2023
Inglese
acute myeloid lekemia, BCL2
BOCCHIA, MONICA
Università degli Studi di Siena
21
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/87482
Il codice NBN di questa tesi è URN:NBN:IT:UNISI-87482