Page 216 - 2021_06-Haematologica-web

N. Oishi et al.
slight increase in growth (14 ± 13% above normoxic base- line, P<0.05, Mann-Whitney test). Silencing CA9 inhibited this growth to 77 ± 6% of normoxic baseline (P<0.001). In TLBR-2, a proposed model of canonical hypoxia response, hypoxia substantially increased growth by 281 ± 79% (P<0.0001) and this increase was reversed nearly to nor-
A
moxic baseline by CA9 silencing (P<0.001 vs. control siRNA). In TLBR-3, which was resistant to hypoxia- induced CA9 expression, no significant increase in growth was induced by hypoxia. In summary, these data indicate that hypoxia-induced growth in BIA-ALCL cell lines fol- lows a pattern similar to that of hypoxia-induced expres-
BC
Figure 2. Breast implant-associated anaplastic large cell lymphomas consistently express CA9. (A) Representative microscopic images of immunohistochemistry for CA9 in breast implant-associated (BIA) anaplastic large cell lymphoma (ALCL), systemic ALK-positive ALCL, systemic ALK-negative ALCL, and primary cutaneous ALCL (40× original magnification). (B) BIA-ALCL show significantly higher CA9 expression than other forms of ALCL. (C) The increased expression of CA9 in BIA-ALCL is independent of genetic subtype. All BIA-ALCL tested have triple-negative (TN) genetics (lacking rearrangements of ALK, DUSP22, and TP63). BIA-ALCL show sig- nificantly higher CA9 expression than ALCL with any of these rearrangements, as well as TN non-BIA-ALCL. ***P<0.001; ****P<0.0001.
1718
haematologica | 2021; 106(6)