Acute Lymphoblastic Leukaemia Review | Assay Genie

Acute lymphoblastic leukaemia (ALL) is one of the most common malignant diseases diagnosed in children. It represents nearly one third of all paediatric cancers and 74% of leukaemic disease in children from age 0-19 years. In 2010 the American Society of Cancer (ACS) predicted that 5,330 new cases of ALL would be detected and that 1,420 of these cases would result in death [Society, 2010].

The cause of ALL remains largely unknown, although potential risk factors include environmental factors, inherited genetic mutations and viral exposure, however, so far no single factor has been definitively shown to cause ALL [Ribera and Oriol,2009]. ALL can develop when a lymphoid progenitor cell becomes genetically altered and undergoes deregulated proliferation, resulting in the altered expression of genes that regulate the development of B-cells and T-cells [Pui and Evans,ÿ1998].

ALL is classified as three different types based on the World Health Organisation [WHO] classification, they are pre-B-cell ALL, which is the most common type of ALL, mature B-cell ALL, and pre-T-cell ALL, although mixed phenotype ALL can also occur [WHO, 2004]. 

The symptoms of ALL include fatigue,fever, weight loss, breathlessness, excessive bruising, anaemia and swollen lymphglands. ALL is diagnosed by white blood cell count, bone marrow biopsy, chest xrayand immunophenotyping. Treatment of ALL requires complex chemotherapy combinations and generally follows a framework developed by the German ALLBFM (Berlin-Frankfurt-Munster) trial, which results in a 75% chance of survival without reoccurrence of cancer [Reiter et al., 1994].

First, induction chemotherapy is used to reduce lymphoblast number in the bone marrow. This treatment requires intravenous administration of the microtubule targeting agent vincristine or the DNA damaging agent daunorubicin in conjunction with oral corticosteroids such as predisolone and anti-metabolites such as l-asparaginase and methotrexate.

Next, consolidation therapy targets drug-resistant leukaemia cells that survive induction therapy using high doses of anti-metabolites mercaptopurine (6-MP) and methotrexate. Finally, maintenance chemotherapy consists of 2 to 3 years of low dose antineoplastic drugs designed to prevent a relapse. Radiation therapy can also be used to kill transformed cells that are not accessible by intravenous chemotherapy [Mattison and Stock, 2008]. Despite the success of current ALL therapeutics there are many associated toxic side effects as many of the drugs target untransformed cells. As such there is a concerted effort to design new chemotherapeutics with specific toxicity towards cancer cells.