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Acute myeloid leukaemia

Abstract

Acute myeloid leukaemia (AML) is a disorder characterized by a clonal proliferation derived from primitive haematopoietic stem cells or progenitor cells. Abnormal differentiation of myeloid cells results in a high level of immature malignant cells and fewer differentiated red blood cells, platelets and white blood cells. The disease occurs at all ages, but predominantly occurs in older people (>60 years of age). AML typically presents with a rapid onset of symptoms that are attributable to bone marrow failure and may be fatal within weeks or months when left untreated. The genomic landscape of AML has been determined and genetic instability is infrequent with a relatively small number of driver mutations. Mutations in genes involved in epigenetic regulation are common and are early events in leukaemogenesis. The subclassification of AML has been dependent on the morphology and cytogenetics of blood and bone marrow cells, but specific mutational analysis is now being incorporated. Improvements in treatment in younger patients over the past 35 years has largely been due to dose escalation and better supportive care. Allogeneic haematopoietic stem cell transplantation may be used to consolidate remission in those patients who are deemed to be at high risk of relapse. A plethora of new agents — including those targeted at specific biochemical pathways and immunotherapeutic approaches — are now in trial based on improved understanding of disease pathophysiology. These advances provide good grounds for optimism, although mortality remains high especially in older patients.

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Figure 1: Schematic overview of the main types of leukaemia.
Figure 2: UK incidence of AML by sex and age.
Figure 3: Age-related survival in England, Sweden and the United States.
Figure 4: Schematic representation of the epigenetic modifiers that are frequently mutated in AML.
Figure 5: Normal and leukaemic haematopoiesis.
Figure 6: Bone marrow smears in AML.
Figure 7: Schematic overview of disease-free survival.
Figure 8: Haematopoietic stem cell transplantation strategies in AML.
Figure 9: Targeting cell signalling to treat AML.

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Contributions

Introduction (A.K. and D.C.L.); Epidemiology (M.B.); Mechanisms/pathophysiology (A.K., D.C.L., R.E.G., R.L.L. and C.T.J.); Diagnosis, screening and prevention (G.E., C.D.B., R.E.G., D.C.L. and A.K.); Management (E.E., A.B., J.J.C., D.A.S. and D.B.); Quality of life (A.K. and D.C.L.); Outlook (D.C.L. and A.K.); Overview of Primer (A.K. and D.C.L.).

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Correspondence to David C. Linch.

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Competing interests

A.K. has received consulting fees from Celgene, Bergen Bio and research funding from AstraZeneca. G.E. has received research grants from Novartis and Celgene and has ownership in GEMoaB Monoclonals. A.B. receives salary from CTI Life Sciences Ltd. D.A.S. is the inventor of antibodies for AML owned by the Sloan Kettering Institute that are licensed to ‘for-profit companies’. D.C.L. has stock and receives salary from Autolus. All other authors declare no conflict of interests.

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Khwaja, A., Bjorkholm, M., Gale, R. et al. Acute myeloid leukaemia. Nat Rev Dis Primers 2, 16010 (2016). https://doi.org/10.1038/nrdp.2016.10

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