Gene rearrangements and translocations in lymphoproliferative diseases.

By Henrik Griesser, Douglas Tkachuk, Marciano D. Reis, and Tak W. Mak L YMPHOID LEUKEMIAS and malignant lymphomas are neoplasms characterized by the proliferation of cells derived from the lymphoid tissue and its precursors. Like other malignant hematological disorders, the majority of these lymphoid malignancies are of monoclonal origin.’ Although clonality does not necessarily correlate with a clinically malignant course of disease, the detection of a clonal population of proliferating cells may help in the discrimination between a reactive process and an autonomous, preneoplastic, or neoplastic lesion.2 The determination of Bor T-cell lineage in these malignant lymphoproliferative disorders has clinical significance. When compared with patients having B-cell malignancies, patients with T-cell malignancies, other than mycosis fungoides, generally tend to have a more aggressive clinical course and poorer response to therapy.3 As an example, cases of T-cell chronic lymphocytic leukemia (T-CLL) with a helper phenotype (CD4 ), or rarer cases of cytotoxic (CD8 ) T-CLL have a poorer prognosis than B-CLL cases.4’5 However, intensified treatment regimens have led to improved remission duration, especially in T-ceii acute lymphoblastic leukemia (T-ALL), where statistically significant differences cannot be demonstrated between the total ALL group and aggressively treated T-ALLs.6 Large clinical trials comparing prognosis of uniformly staged and treated patients with T-cell diffuse large-cell lymphomas and comparable histologic subtypes of B-cell lymphomas are required to ascertain the significance of lymphoma lineage.7 Over the past several years, the increasing availability of highly specific monoclonal antibodies has made it possible to clearly define the lineage and stage of differentiation of a large number of malignant lymphoproliferative disorders.8 Most non-T ALL and mature B cell non-Hodgkin’s lymphomas can be classified using panels of lymphoid-associate markers, which delineate stages of lymphoid differentiation, and antibodies against and A immunoglobulin light chains (IgL), which define clonality, in addition to and combined with the more traditional morphological analysis.8’9 However, if the malignant B cells constitute only a small minority