Molecular Mechanisms of Relapse in Childhood Acute Myeloid Leukemia

By: Habsah Aziz

Leukemia is a type of cancer caused by the unregulated proliferation of a clone of immature blood cells derived from mutant haematopoeitic stem cells (Martin et al., 2002).  It begins in the bone marrow and results in high numbers of abnormal white blood cells. These white blood cells are not fully developed and are called blasts or leukemia cells. Clinically and pathologically, leukemia is subdivided into a variety of large groups. There are four main types of leukemia: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML). AML is characterized by the accumulation of immature myeloblasts as a consequence of arrested myeloid differentiation and a subsequent deficiency in functional mature granulocytes and monocytes.

Great progress has been made in recent years in improving the cure rate of leukemia. However, the challenge of the relapsed disease is still huge as many patients die due to drug resistance or clones which were not responsive to the chemotherapy. The current intensive cytotoxic chemotherapy regimens achieve long-term cure in only 60–70% of patients, and relapsed AML accounts for more than half of childhood leukemia-related deaths (Moore et al. 2013). Relapsed and chemotherapy-refractory AML is thus an area of unmet clinical need and presents opportunities for the development of novel targeted therapeutic approaches.