THE 5Q35BP CHROMOSOMAL ABNORMALITY CHARACTERIZES CERTAIN CD30 POSITIVE ANAPLASTIC LARGE-CELL LYMPHOMAS OFFERING A NEW DEFINITION OF MALIGNANT HISTIOCYTOSIS IN CHILDHOOD

Anaplastic large cell CD30 positive lymphomas represent a heterogeneou s group of lymphomas in which immunocytochemical and molecular investi gations have demonstrated the existence of malignancies of T, B or und etermined origin. The recent identification, in a few cases, of a chro mosomal 5q35 breakpoint may allow distinction of a specific disease. I n these cases, the 5q35bp has been found to be a permanent abnormality present in 5 cell lines and associated with various translocations in cluding most often t(2;5) but also t(7;5), t(5;6) and t(3;5). A primit ive myelomonocytic origin of these 5q35bp cells is suggested on the ba sis of the following arguments: i) they spontaneously express CD68; ii ) they reduce tetrazolium blue; iii) they express the c-fms proto-onco gene which encodes the macrophage growth receptor (CSF-1); iv) c-fms, which is not rearranged, has been mapped to 5q33 close to the 5q35 bre akpoint; v) treatment by phorboldiester of a 5q35bp cell line (DEL) in duces immunodependent phagocytosis and modulation of the expression of c-fms, CSF-1 and TNF alpha. Since some 5q35bp cell lines also present rearrangements of TCR beta or Ig (jH), these data suggest an ancestra l stem-cell origin, prior to T, B or myelomonocytic differentiation. W hatever its origin, the 5q35bp abnormality is mainly encountered in ch ildhood malignancies. As it is constantly associated with the clinical and biological manifestations of a condition recognized by pediatrici ans as malignant histiocytosis, 5q35bp may today represent the best cr iterion for the identification of malignant histiocytosis in childhood .