General AML

Down for the Count in AML: Understanding the Mechanisms By Which AML Blasts Might Induce Cytopenias

In a recent issue of Blood, Aaron D. Goldberg and Martin S. Tallman provided a commentary on the work by Rauch et al. relating to a decline in non-leukemic hematopoiesis in the bone marrow of patients with Acute Myeloid Leukemia (AML).

According to Goldberg and Tallman the majority of patients with AML present with cytopenias in 1 or more cell lineages. Yet, despite many hypotheses, the mechanism by which healthy hematopoiesis is disrupted in AML still needs to be elucidated.

The research by Rauch et al. provided further understanding of the mechanisms by which AML blasts might induce cytopenias. Primarily their findings challenged the notion that AML spatially displaces non-leukemic hematopoiesis from the bone marrow. They reported that, based on the examination of 223 AML patients, they did not identify a relationship between bone marrow blast content and cytopenia. However, they do state that cytopenia is strongly predicted by MPL expression on blast cells.

They further investigated the pathogenesis of peripheral blood cytopenia by measuring the serum concentration Thrombopoietin (TPO), the regulator of hematopoietic stem cells and megakaryocytes. They reported that MPLhi blasts scavenge TPO from the serum, which results in insufficient cytokine levels for non-leukemic hematopoiesis.

However, Tallman and Goldberg do not believe that TPO scavenging by MPL is the only determinant of cytopenias in AML patients. Although, they still affirm that the research by Rauch et al. of great significance for the following reasons:

“[The research] supports an intriguing and novel model to explain the impairment of normal hematopoiesis in patients with AML. By stealing TPO, high levels of MPL on AML blasts might leave AML patients down for the count.”

The full article by Goldberg Tallman from Blood can be found here

References
  1. Goldberg A.D. & M.S. Tallman. Down for the count in acute myeloid leukemia. Blood. 2016; 128:2195–2197. DOI:10.1182/blood-2016-09-738765.
  2. Rauch P.J. et al. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia. Blood. 2016 128:2253-2257; DOI:10.1182/blood-2016-04-711986