Leukaemia Biology Debate: AML Focus

AML reveals a complex interplay between malignant cells and their environment where disease progression and treatment response is orchestrated.

The following is a summary of the article “Acute myeloid leukaemia: First debate on leukaemia biology” by Antonio Curti (IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy), which is part of the Proceedings of the 4th European Congress controversies in Leukemias, held in Brussels, Belgium, 20-21 November, 2023.

Delving into the complexities of Acute Myeloid Leukaemia (AML) reveals a multifaceted battleground where the interplay between malignant cells and their environment orchestrates disease progression and treatment response. Representing a significant portion of adult leukaemia cases, AML presents unique challenges due to its heterogeneity and the intricate web of cellular and molecular interactions within the bone marrow microenvironment.

Despite advancements in understanding its genetic underpinnings, AML remains notoriously difficult to treat, with dismal prognosis particularly in older patients. However, a deeper comprehension of the leukemic microenvironment (LME) is shedding light on potential avenues for therapeutic intervention.

The latest insights, elucidated at the prestigious EUROLEUK 2023 conference, unravel the enigmatic relationship between AML cells and their surroundings. Pioneering research showcased during the event underscored the pivotal role of the immune system in shaping AML progression and response to therapy.

Notably, immune-suppressive cell populations were identified as architects of a hostile milieu, impeding the anti-leukaemia immune response and fostering therapeutic resistance. Furthermore, the intricate crosstalk between non-immune cellular elements and leukemic cells emerged as a crucial determinant of disease trajectory.

Mesenchymal stromal cells (MSCs), pivotal regulators of hematopoietic stem cell differentiation and bone marrow architecture, were spotlighted for their intricate involvement in supporting leukaemia cell survival and immune evasion. This intricate dance between MSCs and AML cells highlights a novel avenue for therapeutic exploration, offering hope for disrupting the tumour-supportive microenvironment.

Yet, despite these revelations, the full spectrum of interactions within the AML microenvironment remains elusive. The dynamic interplay between immune and non-immune cells, coupled with the impact of somatic mutations on immune modulation, underscores the complexity of AML pathogenesis. This complexity, however, presents an opportunity for paradigm-shifting approaches to classification and treatment stratification.

EUROLEUK 2023's discussions didn't merely stop at unveiling the intricacies of AML's microenvironment; they paved the way for future research directions and therapeutic innovations. By integrating genomic profiling with immune landscape characterisation, a more nuanced understanding of AML's immunobiology is within reach. Moreover, lessons gleaned from allogeneic hematopoietic stem cell transplantation underscore the intertwined nature of clonal and immune cell dynamics, offering insights into both therapeutic successes and failures.

The insights gleaned from EUROLEUK 2023 serve to help us inch closer to personalised therapies and improved outcomes for patients with AML.

For the full text article published by Medicom Medical Publishers, see Curti A. Proceedings of the 4th European Congress Controversies in Leukemia,  Brussels, Belgium, 20-21 November, 2023. https://doi.org/10.55788/5f3943ab