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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3567-3574.
Prepublished online as a Blood First Edition Paper on July 26, 2005; DOI 10.1182/blood-2005-02-0519.
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Submitted February 8, 2005
Accepted July 11, 2005
CD94 1A transcripts characterize lymphoblastic lymphoma/leukemia of immature natural killer cell origin with distinct clinical features
Chung-Wu Lin, Ting-Yun Liu, Shee-Uan Chen, Kun-Teng Wang, L J Medeiros, and Su-Ming Hsu*
Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
Department of Obsterics & Gynecology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
* Corresponding author; email: smhsu2003{at}yahoo.com.
Most lymphoblastic lymphomas (LBLs) are regarded as neoplasms of immature T-cells because they express cytoplasmic CD3 and frequently carry T-cell receptor (TCR) gene rearrangements. Immature natural killer (NK)- and T-cells, however, have a common bipotent T/NK-cell precursor in the thymus and NK-cells also express cytoplasmic CD3. Thus, some LBLs could arise from immature NK-cells. Mature NK-cells express two CD94 transcripts: 1A, induced by IL-15, and 1B constitutively. Since immature NK-cells require IL-15 for development, CD94 1A transcripts could be a marker of NK-LBL. To test this hypothesis, we used laser capture microdissection to isolate IL-15 receptor + lymphoid cells from the thymus and showed that these cells contained CD94 1A transcripts. We then assessed for CD94 transcripts in 21 cases of LBL that were cytoplasmic CD3+, nuclear TdT+, and CD56-, consistent with either the T- or NK-cell lineage. We found that 7 LBLs expressed CD94 1A transcripts without TCR gene rearrangements, suggesting NK-cell lineage. Patients with NK-LBL were younger than patients with T-LBL (15 years versus 33 years; p=0.11) and had a better 2-year survival (100% versus 27%; p< 0.01). These results improve the current classification of LBL and contribute to our understanding of NK-cell differentiation.

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