Subset of T-Cell Prolymphocytic Leukemia Expresses CD117. Potential Target for Therapy.

Introduction

Excluding non-hematopoietic lesions, CD117 (c-kit) is expressed by erythroid, megakaryocytic and myeloid precursors, mature mast cells, subset of plasma cell neoplasm and occasional precursor lymphoblastic tumors. C-kit plays important role in T-cell development around birth, but the expression of CD117 in mature T-cell lymphoproliferations is rare. We present flow cytometry phenotypic data of 28 cases of T-cell prolymphocytic leukemia (T-PLL).

Material and methods

Multiparameter 4-color FC analysis was performed on peripheral blood and/or bone marrow aspirate samples using the following antibodies: CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD13, CD14, CD16, CD19, CD20, CD25, CD33, CD34, CD38, CD45, CD56, CD64, CD79a, CD117, TCRab/γδ, TdT, and HLA-DR. Fresh bone marrow aspirates and/or peripheral blood films and cytospin preparations from FC samples were stained with Wright-Giemsa.

Results

T-PLL was diagnosed 28 cases. The ages ranged from 43 to 92 years. Normal expression of pan-T cell antigens (CD2, CD3, CD5, CD7) was present in 57%. Abnormal expression of one, two and three antigens was noted in 21%, 11% and 11%, respectively. 4 cases showed aberrant expression of CD117. Those cases were always CD8-positive (50% of T-PLL were CD4+). There were no pan-myeloid (CD13, CD33) and blastic (TdT, CD34) markers present. Molecular studies confirmed clonal rearrangement of TCR.

Discussion

T-PLL is rare mature T-cell neoplasm characterized by marked lymphocytosis of small to medium-sized cells with conspicuous nucleoli. The response to conventional chemotherapy in T-PLL, similarly to other mature T-cell lymphoproliferations (except ALK+ anaplastic large cell lymphoma) generally is poor. While the use of alemtuzumab (Campath-1H) has improved remissions, the disease remains incurable. Novel treatment approaches, tailored to individual patients, and based on pathologic, phenotypic and molecular features will be crucial to improve survival for the patients with this disease.

Based on the flow cytometry analysis of 28 cases of T-PLL we identified 4 cases with co-expression of CD117 (14%). When present, it is restricted to CD8+ tumors. We speculate that the expression of CD117 (c-kit) in these patients apart from its diagnostic utility, may serve as a criterion for a combination therapy with Campath-1H and imatinib mesylate.