Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features.

Introduction: Mantle cell leukemia (MCLeu) has been considered as a leukemic form ofmantle cell lymphoma (MCL). However, the presence of certain features rarely observed inMCL, such as transformation to prolymphocytic leukemia (PLL) or indolent clinical course,suggests that MCLeu may represent a distinct disorder.Methods: Seven cases of MCLeu with t(11;14)(q13;q32) and BCL1-IGH gene rearrangementwere ascertained among 140 newly diagnosed chronic B-cell lymphoproliferative disorderswith leukemic expression. Comparative genomic hybridization, FISH for specific gene loci,and immunological studies were preformed in them.Results: In comparison with CLL, MCLeu cases had low immunological scores 42 withrespect to B-CLL (P50.0001). Expression of CD38 was absent in 43% of MCLeu and in44% of B-CLL. Comparative genomic hybridization analysis identified genomic imbalances in86% of MCLeu with a similar pattern than in MCL: gains of 3q, 8q involving MYC gene and15q, and losses of 6q, 9p, 13q and 17p a•ecting P53 gene. Di•erently from MCL and CLL,genomic loss of 8p was frequently detected in MCLeu (83%). Although clinical presentationof MCLeu was indistinguishable from CLL, all patients but one had disease progressionwithin three years. According to the immunologic and genomic profiles, two distinctsubgroups of MCLeu were defined: one related to PLL, showing CD38-, deletion of P53, andMYC amplification and another which corresponds to a leukemic form of classical MCL,presenting with CD38+ and normal P53 and MYC status.Conclusion: MCLeu and MCL are closely related disorders, as they show similar genomicand molecular patterns. However, the deletion of the short arm of chromosome 8 mayrepresent a specific marker for MCLeu. Two distinct subgroups of MCLeu may also bedistinguished according to the immunologic and genomic cell profiles.The Hematology Journal (2001) 2, 234–241Keywords: mantle cell leukemia; BCL1-IGH; MYC amplification; P53 deletion; CD38