Understanding AML: Pathophysiology, Presentation, and Diagnostic Workup

Welcome back to another AJMC Peer Exchange series. In "Understanding AML: Pathophysiology, Presentation, and Diagnostic Workup," moderator Zahra Mahmoudjafari, PharmD, BCOP, FHOPA, MBA is joined by Guru Murthy, MD, MS, Amir Zeidan, MBBS, MD, and Eytan Stein, MD to open the series on acute myeloid leukemia with a focused look at disease biology and diagnosis.

Dr. Mahmoudjafari, director of pharmacy at the University of Kansas Cancer Center, introduces the panel. She frames the program around optimizing AML management, with a special focus on oral therapy integration, real-world access, and adherence. She opens the first section by asking Dr. Murthy to describe the underlying pathophysiology of AML in a few sentences.

Dr. Murthy explains that AML results from an accumulation of myeloid blasts and is fundamentally a stem cell disorder. A founder or driver mutation typically initiates the disease at the stem cell level. Clonal expansion then follows under selective pressure, ultimately driving proliferation of the malignant clones. He notes that the initial trigger usually remains unknown. Older age is associated with a greater burden of mutations linked to malignancy. Prior chemotherapy or radiation may contribute in some patients. For the vast majority, however, the cause is still not identified.

Dr. Zeidan then addresses diagnosis and the differential. He observes that AML is rarely confused with other conditions and is usually a straightforward diagnosis. Patients tend to present in one of two ways. Some arrive acutely ill in the emergency department, occasionally with respiratory failure caused by blast accumulation in the lungs. Others have a more indolent presentation, with gradually declining blood counts that eventually prompt a bone marrow biopsy. Flow cytometry is a common diagnostic tool, and the diagnosis can sometimes be made from peripheral blood alone. Genetic testing is performed not only to confirm the diagnosis but also to define the subtype. It increasingly directs treatment, which has become highly targeted. Bone marrow biopsy is still needed in many patients. He adds that other myeloid malignancies, such as myelodysplastic syndromes or myelofibrosis, can occasionally resemble AML, but true diagnostic confusion is uncommon.

Our next episode, "AML Risk Stratification and Fitness Assessment: ELN Systems and Objective Criteria," turns to Dr. Stein's view of the ELN risk systems and Dr. Murthy's approach to objectively defining fitness.