Hairy cell leukemia associated with large granular lymphocyte leukemia: immunologic and genomic study, effect of interferon treatment

Abstract

The authors describe a patient who presented an association of hairy cell leukemia (HCL) and large granular lymphocyte (LGL) leukemia. An eventual relationship between these two rare entities is analyzed. Hairy cells (HCs) were present in the blood, bone marrow, and spleen. An excess of LGLs was found only in the blood and bone marrow. After splenectomy the patient received an alpha 2-interferon (alpha 2-IFN) treatment. The HCs surface phenotype was mu+delta+kappa+, CD20+, and CD25+. The LGLs consisted in CD3+, CD8+, HNK1+, WT31+ T lymphocytes. These were absent in the spleen. alpha 2-IFN treatment resulted in the disappearance of the HCs in the blood and bone marrow, whereas the LGLs remained unchanged. Before alpha 2-IFN treatment, peripheral blood cells, predominantly LGLs, exerted low cytotoxicity that increased up to a normal level after treatment. Using Southern blotting the authors studied the rearrangements of the T-cell receptor beta--chain (C beta) and gamma-chain (J gamma) genes and immunoglobulin heavy (JH)- and light (C kappa, C lambda)- chain genes. An unique JH and C kappa gene rearrangement was found in the blood and spleen, whereas C beta and J gamma gene rearrangements were present in the blood, not in the spleen. Under alpha 2-IFN treatment, the JH gene rearrangement fainted dramatically, in contrast to that of the C beta gene. The study of messenger RNA (mRNA) of the T cell receptor alpha and beta chains evidenced the 1.3-kilobase (kb) and 1.6-kb bands in the blood and their absence in the spleen. The patient was human T-cell leukemia virus (HTLV)-II negative by Southern analysis of blood and spleen cells. It is concluded that the LGL expansion was clonal and not reactive to the HCL. Although the authors cannot definitely exclude that both HC and LGL proliferations stem in a common leukemic precursor, their findings support an association of the two entities.

Coincident myelodysplastic syndrome and T‐cell large granular lymphocytic disease: clinical and pathophysiological features

“…Limited studies indicate that T‐LGL cells inhibit autologous myeloid progenitors and clinical reports indicate that a high proportion of patients respond to cyclosporin immunosuppression with significant improvement of anaemia and neutropenia (Sood et al , 1998; Molldrem et al , 1999). T‐LGL is associated with autoimmune diseases such as rheumatoid arthritis (Loughran et al , 1988; Marolleau et al , 1988; Amparo et al , 1991; Dhodapkar et al , 1994; Semenzato et al , 1997). T‐LGL has also been reported to be associated with MDS; in addition to a single case report associating T‐LGL with MDS (Bassan et al , 1987), five patients were noted to have MDS in a review of 68 patients with T‐LGL (Dhodapkar et al , 1994).…”

Clinicopathological analysis of a composite lymphoma containing both T‐ and B‐cell lymphomas

“…While many of these cases are composed of Hodgkin's and non‐Hodgkin's components, 5–14 others represent different types of non‐Hodgkin's lymphoma from the same lineage 15–18 . Examples of CTBL have also been documented, 19–40 and the components involved in these CTBLs have been shown to vary from one case report to another.…”

Association of B-chronic lymphocytic leukaemia and T-large granular lymphocyte leukaemia

“…Association between LGL and B‐cell lymphoproliferative disorders is uncommon. Hairy cell leukaemia, multiple myeloma and monoclonal gammapathy, non‐Hodgkin’s lymphoma and Hodgkin’s disease have been occasionally reported to be associated with LGL leukaemia ( Marolleau et al. 1988; Bassan et al.…”