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

Hematol J. 2001;2(4):234-41. doi: 10.1038/sj.thj.6200111.

Abstract

Introduction: Mantle cell leukemia (MCLeu) has been considered as a leukemic form of mantle cell lymphoma (MCL). However, the presence of certain features rarely observed in MCL, 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 rearrangement were ascertained among 140 newly diagnosed chronic B-cell lymphoproliferative disorders with 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 < or =2 with respect to B-CLL (P<0.0001). Expression of CD38 was absent in 43% of MCLeu and in 44% of B-CLL. Comparative genomic hybridization analysis identified genomic imbalances in 86% of MCLeu with a similar pattern than in MCL: gains of 3q, 8q involving MYC gene and 15q, and losses of 6q, 9p, 13q and 17p affecting P53 gene. Differently from MCL and CLL, genomic loss of 8p was frequently detected in MCLeu (83%). Although clinical presentation of MCLeu was indistinguishable from CLL, all patients but one had disease progression within three years. According to the immunologic and genomic profiles, two distinct subgroups of MCLeu were defined: one related to PLL, showing CD38-, deletion of P53, and MYC 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 genomic and molecular patterns. However, the deletion of the short arm of chromosome 8 may represent a specific marker for MCLeu. Two distinct subgroups of MCLeu may also be distinguished according to the immunologic and genomic cell profiles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Aged
  • Antigens, CD*
  • Antigens, Differentiation / metabolism
  • Chromosome Aberrations
  • Chromosome Deletion
  • Chromosomes, Human, Pair 8 / genetics
  • Diagnosis, Differential
  • Female
  • Genes, myc
  • Genes, p53
  • Humans
  • Leukemia / classification*
  • Leukemia / diagnosis*
  • Leukemia, Prolymphocytic / etiology
  • Lymphoma, Mantle-Cell / classification
  • Lymphoma, Mantle-Cell / diagnosis*
  • Lymphoproliferative Disorders / classification
  • Lymphoproliferative Disorders / diagnosis
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • NAD+ Nucleosidase / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Membrane Glycoproteins
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1