Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide

Ayalew Tefferi, Philip R. Greipp, Paul J. Leibson, Stephen N. Thibodeau

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characterstics of either cytotoxic T lymphocytes (CD3+ ,CD8+) or natural killer (NK) cells (CD3-,CD16+). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK celts do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked DNA analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16- immunoconjugated magnetic beads. The DNA of these ceils was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.

Original languageEnglish (US)
Pages (from-to)477-480
Number of pages4
Issue number5
StatePublished - May 1992

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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