Adult Acute Lymphoblastic Leukemia Treatment (Professional) (cont.)
IN THIS ARTICLE
Cellular Classification of Adult ALL
The following leukemic cell characteristics are important:
In adults, French-American-British (FAB) L1 morphology (more mature-appearing lymphoblasts) is present in fewer than 50% of patients, and L2 morphology (more immature and pleomorphic) predominates. L3 (Burkitt) ALL is much less common than the other two FAB subtypes. It is characterized by blasts with cytoplasmic vacuolizations and surface expression of immunoglobulin, and the bone marrow often has an appearance described as a "starry sky" owing to the presence of numerous apoptotic cells. L3 ALL is associated with a variety of translocations that involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus t(2;8), t(8;12), and t(8;22).
Some patients presenting with acute leukemia may have a cytogenetic abnormality that is morphologically indistinguishable from the Philadelphia chromosome (Ph1). The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of adults and a small percentage of children with ALL. In the majority of children and in more than one-half of adults with Ph1-positive ALL, the molecular abnormality is different from that in Ph1-positive chronic myelogenous leukemia (CML).
Many patients who have molecular evidence of the bcr-abl fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics. The bcr-abl fusion gene may be detectable only by pulsed-field gel electrophoresis or reverse-transcriptase polymerase chain reaction for the bcr-abl fusion gene because many patients have a different fusion protein from the one found in CML (p190 vs. p210).
Table 1. Frequency of ALL Cell Subtypes
About 95% of all types of ALL (except Burkitt, which usually has an L3 morphology by the FAB classification) have elevated terminal deoxynucleotidyl transferase (TdT) expression. This elevation is extremely useful in diagnosis; if concentrations of the enzyme are not elevated, the diagnosis of ALL is suspect. However, 20% of cases of AML may express TdT; therefore, its usefulness as a lineage marker is limited. Because Burkitt leukemias are managed according to different treatment algorithms, it is important to specifically identify these cases prospectively by their L3 morphology, absence of TdT, and expression of surface immunoglobulin. Patients with Burkitt leukemias will typically have one of the following three chromosomal translocations:
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