Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

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Baliakas, Panagiotis | Agathangelidis, Andreas | Hadzidimitriou, Anastasia, C | Sutton, Lesley-Ann | Minga, Eva | Tsanousa, Athina | Scarfò, Lydia | Davis, Zadie | Yan, Xiao-Jie | Shanafelt, Tait | Plevova, Karla | Sandberg, Yorick | Juhl Vojdeman, Fie | Boudjogra, Myriam | Tzenou, Tatiana | Chatzouli, Maria | Chu, Charles | Veronese, Silvio | Gardiner, Anne | Mansouri, Larry | Smedby, Karin Ekström | Pedersen, Lone Bredo | Moreno, Denis | van Lom, Kirsten | Giudicelli, Véronique | Skuhrova Francova, Hana | Nguyen-Khac, Florence | Panagiotidis, Panagiotis | Juliusson, Gunnar | Angelis, Lefteris | Anagnostopoulos, Achilles | Lefranc, Marie-Paule | Facco, Monica | Trentin, Livio | Catherwood, Mark | Montillo, Marco | Geisler, Christian | Langerak, Anton | Pospisilova, Sarka | Chiorazzi, Nicholas | Oscier, David | Jelinek, Diane | Darzentas, Nikos | Belessi, Chrysoula | Davi, Frederic | Ghia, Paolo | Rosenquist, Richard | Stamatopoulos, Kostas

Edité par CCSD ; American Society of Hematology -

International audience. An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non–subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non–subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non–subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non–subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

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