Acute Lymphocytic Leukemia - Prognosis

Cytogenetics is a technique that researchers use to determine specific genetic abnormalities, which are found in nearly 65% of all leukemias. Detecting these genetic defects is helpful in making a full diagnosis of ALL and in planning the most appropriate therapy. Specific technologies called microarray chips are now capable of checking up to 48,000 different genes in a single experiment, which holds promise for assessing prognosis and developing very targeted therapies in the future. Research on DNA microarray analysis continues to reveal different prognostic subgroups of ALL. As the precision, logistics, and cost effectiveness of DNA microarray assays improve, they may be used more commonly in the clinical setting.

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MTHFR Variants. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism, and variations in the MTHRF gene may also influence response to antifolate chemotherapy. A 2004 study showed that patients with one of two specific variations of the MTHFR gene had a lower probability of survival following treatment with methotrexate.

Translocations. Genetic translocations (swapping of genes on chromosomes) may affect outlook. Examples include the following:

Patients with the t(12;21) genetic translocation (also referred to as TEL-AML1 fusion) have an excellent prognosis.
Patients who carry the defective gene called ETV6 often respond well to chemotherapy.
The t(4;11), sometimes referred to as MLL, is the most common translocation in children under one year. Unfortunately, it carries a poor outlook in anyone who carries it. A 2001 study suggested that this genetic variant may actually be a unique leukemia and require treatments that differ from standard ALL.
The Philadelphia translocation also t(9;22) indicates a poor outlook. It represents about 20% of adult cases and only about 5% of childhood cases.
The t(1;19) location occurs in about 5% of ALL childhood cases and requires aggressive treatment.

Ploidy. Ploidy refers to the number of chromosomes. Additional copies (hyperdiploidy) or absence of copies (hypodiploidy) of chromosomes affect prognosis. For example, in children hyperdiploidy is associated with a more favorable outcome and hypodiploidy with a poorer outcome. (Hypodiploidy occurs only in 1% of children with ALL.)

Morphology

The morphology of a cell includes its physical characteristics, such as shape and structure. To determine the morphology of the leukemia cells, samples of the bone marrow are taken and particular contents of the cells are stained with a dye. They are then examined under a microscope.