Acute myeloid leukemia (AML) is a malignant cancer characterized by the infiltration of bone marrow by proliferative, abnormally differentiated, heterogeneous, clonal hematopoietic stem cells (HSCs), leading to bone marrow failure, and ultimately death if untreated.1
These abnormal white blood cells progressively occupy the bone marrow niche, where healthy HSCs ordinarily reside and are maintained.2 Emerging evidence suggests that leukemic cells induce molecular changes in hematopoietic cells, contributing to the transformation of the normal bone marrow niche into a ‘leukemia’ niche, allowing the growth and proliferation of leukemic cells, disrupting the ordinary functioning of HSCs.3
To classify the disease, morphological assessments are carried out on bone marrow and the blood is analyzed for the expression of cytoplasmic markers using flow cytometry.4 Major categories of AML include therapy-related AML, AML with myelodysplasia-related changes, AML with recurrent genetic abnormalities and AML otherwise not specified.5
Current therapies include induction therapy, consolidation therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), with those ineligible for intensive therapy receiving supportive care, low-dose cytarabine and the hypomethylating agents, azacitidine and decitabine. Targeted therapy drugs have also been introduced in recent years, with a ficus on FLT3 and IDH inhibitors.
The AML Global Portal has reported on drugs that have recently been approved, or are in the process of being approved:
- FDA grants ivosidenib Breakthrough Therapy Designation
- Regulatory review granted by EMA for gilteritinib
- FDA approves gilteritinib to treat relapsed or refractory AML with FLT3 mutation
- FDA grants venetoclax approval to treat newly diagnosed AML
- NICE recommends gemtuzumab ozogamicin for patients with untreated CD33+ AML
Over the last year, the AML Global Portal has reported on drug approvals around the world:
- 23 April: European Commission grants approval for gemtuzumab ozogamicin for previously untreated CD33-positive AML
- 23 May: Australian Department of Health approves midostaurin to treat newly diagnosed FLT3+ AML patients
- 21 November: FDA approves glasdegib to treat newly diagnosed AML patients ineligible for intensive chemotherapy
- 21 November: FDA grants approval for venetoclax to treat patients newly diagnosed with AML
- 28 November: FDA approves gilteritinib to treat relapsed/refractory FLT3+ AML patients
Despite the development of optimal therapeutic approaches, such as intensive chemotherapy and allogeneic HSC transplantation, only a minority of patients are cured successfully. Thus, designing and developing more effective therapeutic approaches, that target key molecular mechanisms driving pathogenesis, to improve clinical outcomes is desirable.
Please visit www.know-aml.com for more information about AML World Awareness Day.
- Burnett, A., Wetzler, M. and Lowenberg, B., Therapeutic advances in acute myeloid leukemia. J Clinical Oncology, 2011 Jan 10, 29(5):487-494.
- Morrison, S.J. and Scadden, D.T., The bone marrow niche for haematopoietic stem cells. Nature, 2014 Jan 15, 505(7483):327.
- Kumar, B., et al. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia, 2017 Aug 17, 32(3):575.
- Döhner, H., et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood, 2010 Jan 21, 115(3):453-474.
- Döhner, H., et al, Acute myeloid leukemia. New England Journal of Medicine, 2015 Sep 17, 373(12):1136-1152.