Leukemic non-nodal mantle cell lymphomas have a distinct phenotype and are associated with deletion of PARP1 and 13q14.

Leukemic non-nodal mantle cell lymphoma (lMCL) is a particular subtype of mantle cell lymphoma (MCL), characterized by leukemic non-nodal disease and slow progression. Recognition of this entity is relevant to avoid overtreatment. Despite indolent clinical behaviour, lMCL might transform to a more aggressive disease. The purpose of this study was to compare lMCL with classical MCL (cMCL) and aggressive MCL (aMCL) using immunohistochemistry, interphase fluorescence in situ hybridization (FISH), and array-based comparative genomic hybridization, in order to identify biomarkers for lMCL diagnosis and prognosis. Seven lMCL patients were included. All had bone marrow involvement without lymphadenopathy. An lMCL phenotype was distinct from that of cMCL and aMCL: SOX11-, ATM+, PARP1+/-, and low KI67 (average 2 %). Beyond the t(11;14) translocation, fewer secondary cytogenetic alterations were found in lMCL compared to cMCL and aMCL, including deletion of PARP1 and 13q14. At last follow-up, one patient with lMCL had died of disease and another had progressive disease. These patients were respectively 13q14 deletion- and PARP1-positive. One other case of lMCL harbored a 13q14 deletion associated with PARP1 deletion. This patient had indolent disease. lMCL has a particular phenotype and fewer secondary cytogenetic alterations than cMCL and aMCL. PARP1 protein expression and 13q14 deletion are associated with a progressive clinical course of lMCL and should be included in initial diagnostic studies as predictors of unfavorable outcome. PARP1 deletion is involved in lMCL pathogenesis and might confer advantage.