AML-7: The impact of gender on genetic aberrations and clinical outcomes in AML

AML, HARMONY, Leukemia

HARMONY Alliance Research Project title: The impact of gender on genetic aberrations and clinical outcome in Acute Myeloid Leukemia.

Challenge

The incidence and treatment outcomes of cancer, including Acute Myeloid Leukemia (AML), have shown to differ between genders. AML with antecedent hematological disease was shown to be more common in males, while treatment-related AML occurs more often in women. Furthermore, men presented inferior overall survival compared to women in a multivariate analysis and have shown different responses to some therapies. Despite this, the gender of cancer patients is rarely taken into consideration in clinical practice. The evidence base pointing to the contribution of biological factors is growing, but these factors are poorly characterized and studies which address gender-related differences are limited. Therefore, there is an unmet need for large-scale studies which specifically focus on gender-associated differences between patients with hematological malignancies.

Project Leadership

Jesse Tettero, Amsterdam UMC

"At the moment there are no treatment differences between the genders, although there are indications that there are (subtle) differences. With this large dataset, we have the unique opportunity to further explore these differences.Due to the amount of patient in the HARMONY Alliance Big Data Platform, we are able to find differences in subpopulations which can be used to tailor the treatment for specific patients”.

Impact

To better understand the underlying causes of gender-related differences between AML patients.
To facilitate gender-tailored adjustments to treatment strategies and utilisation of prognostic factors to correct for potential gender-specific effects, thereby enabling more patient-tailored clinical management of AML.

Project Summary

The current project will identify and evaluate gender-related differences in genetic and clinical features of a large cohort of AML patients within the HARMONY consortium. Additionally, the project will investigate if targeted treatment varies between men and women. A dataset of 5,000 characterized samples will be split by subgroup (gender) and analyzed. Overall, the study will consist of three key steps:

The clinical characteristics of men and women diagnosed with AML will be identified and compared (ie, white blood count, platelet counts, age at diagnosis and morphology).
Gender-related differences in clinical and genetic aberrations will be determined and the variation occurrence and prognostic value will be evaluated between genders.
The difference between genders, if any, in clinical outcome to standard chemotherapy protocols and targeted treatments will be analyzed. A survival analysis will be completed.

This project will be the largest up-to-date study (to our knowledge) which will focus specifically on gender-related differences in AML. The over-arching goal is to identify gender-related genetic and clinical differences, potentially leading to improvements in the gender-specific treatment of AML patients.

Results

EHA 2024 Congress Abstract P442: SEX DISPARITIES IN GENETIC LANDSCAPE OF ACUTE MYELOID LEUKEMIA: A COMPREHENSIVE ANALYSIS USING THE HARMONY CONSORTIUM DATASET Link >

Presenter: Jesse Tettero, Amsterdam UMC
Author(s) / HARMONY Alliance Partners: Jesse Tettero, Daniele Dall'Olio, Luciana Carota, Amin Turki, Eric Sträng, María Abáigar Alvarado, Martje Barbus, Axel Benner, Frederik Damm, Javier Elicegui, Alberto Hernandez-Sanchez, Soren Lehmann, Joaquín Martinez-Lopez, Rosa Ayala Diaz, Rabea Mecklenbrauck, Klaus Metzeler, Ken Mills, Renate Schulze Rath, Jordi Sierra Gil, Marta Sobas, Ian Thomas, Laura Tur, Peter Valk, Jurjen Versluis, Jacqueline Cloos, Nigel Russell, Christian Thiede, Guillermo Sanz, Konstanze Döhner, Michael Heuser, Torsten Haferlach, Jesus Hernández Rivas, Brian Huntly, Gert Ossenkoppele, Hartmut Döhner, Gastone Castellani, Lars Bullinger

Public-private partnership for Big Data in Hematology

HARMONY and HARMONY PLUS are funded through the Innovative Medicines Initiative (IMI), Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. Funding is received from the IMI 2 Joint Undertaking and is listed under grant agreement for HARMONY No. 116026 and grant agreement for HARMONY PLUS No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA).