T‐cell large granular lymphocytic leukemia and hereditary hemochromatosis: A fortuitous association?

Abstract

We describe a patient with hereditary hemochromatosis (homozygous for C282Y mutation) and neutropenia who was found to have underlying T‐cell large granular lymphocytic (T‐LGL) leukemia. The diagnosis was confirmed by demonstrating T‐cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR). Multiple quantitative and qualitative defects have been described for the T cells of patients with hemochromatosis. Although the association between the two may be fortuitous, this case report raises the possibility that the T cells in these patients may be susceptible to leukemic transformation as well. Am. J. Hematol. 78:299–301, 2005. © 2005 Wiley‐Liss, Inc.

The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders

“…Other hematological conditions associated with LGL leukemia patients have also been reported, including hereditary hemochromatosis [102, 103], splenic marginal zone lymphoma [50], peripheral T lymphoma [104], familial (congenital) pancytopenia with interstitial pneumonia [105] and Wiskott-Aldrich syndrome (WAS) [106–108]. Among these, the association between WAS and LGL leukemia represents another possible pathogenic mechanism.…”

The novel SLC40A1 (T419I) variant results in a loss-of-function phenotype and may provide insights into the mechanism of large granular lymphocytic leukemia and pure red cell aplasia

“…23 However, the detailed pathophysiology still remains to be clarified. In some previously reported cases, LGLL and PRCA are alone or simultaneously associated with rheumatoid arthritis, 24 type 1 and 2 autoimmune polyglandular syndrome, 25,26 and hemochromatosis, 27 all of which are partially or completely similar with symptoms of iron overload. All of these indicated that these diseases may not just a fortuitous but a pathological association.…”

What is Your Diagnosis?

“…Moreover, there have been reports in human medicine that describe a possible association between hereditary hemochromatosis and lymphocytic leukemia. 16 Iron may contribute to carcinogenesis, because it is an essential nutrient for proliferating cells and it aids in producing hydroxyl radicals. 16,17 Whether the two conditions are associated or not, the owner of this bird was informed that starlings should be fed an iron-restricted diet because of their predisposition to iron storage disease.…”