Anti-DUSP22 (aa 112-184) polyclonal antibody

Intravascular large B-cell lymphomas and EBV+ NK/T-cell lymphomas commonly follow an aggressive clinical course. We recently reported an entirely intravascular anaplastic large cell lymphoma (ALCL) in the skin with a surprisingly indolent clinical course; interestingly, this lymphoma involved the lymphatic rather than the blood vasculature. We hypothesized that intravascular skin-limited ALCL is distinct from aggressive systemic intravascular lymphomas in its intralymphatic localization and clinical course. We now describe 18 cases of cutaneous intravascular large cell lymphoproliferations from 4 institutions. All 12 intravascular large T-cell lesions were intralymphatic; the majority (9) were CD30(+) T-cell lymphoproliferative disorders (TLPDs), 5 further classified as intravascular ALK(-) ALCL. One ALK(+) ALCL and 2 benign microscopic intravascular T-cell proliferations were also intralymphatic. A single case of otherwise typical cutaneous follicle center lymphoma contained intralymphatic centroblasts. The clinical and pathologic characteristics of the CD30(+) TLPDs were similar to those of their extravascular counterparts, including extralymphatic dermal involvement in a subset, DUSP22-IRF4 translocations in half of tested ALK(-) ALCLs, and associated mycosis fungoides in 1; most were skin-limited at baseline and remained so at relapse. All 5 cases of intravascular large B-cell lymphoma involved the blood vasculature and behaved in a clinically aggressive manner; the ALK(+) ALCL, although intralymphatic, was systemic and clinically aggressive. We propose that cutaneous ALK(-) ALCL and related CD30(+) ALK(-) TLPDs involving the lymphatics are part of an expanding spectrum of CD30(+) TLPDs. The identification of intralymphatic as distinct from blood vascular localization may provide critical prognostic and therapeutic information.

The Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) is a nonreceptor protein tyrosine phosphatase (PTP) involved in extracellular-regulated kinase (ERK) activation. Recent studies have shown that gain-of-function mutations in SHP-2 are associated with several diseases, including LEOPARD syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. In this study, we identified the novel SHP-2 inhibitor 3-(1-benzimidazolylmethyl)-6-p-tolyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (MLS-001). SHIP-2 activity was inhibited by MLS-001, whereas other types of PTPs, namely ACP1, CDC25A, DUSP3, DUSP14, DUSP18, DUSP22, DUSP23, DUSP26, and SSH3, were not. Furthermore, TCPTP and SHP-1 that are closely related to SHP-2 were not inhibited by the inhibitor. Kinetic studies with MLS-001 and SHP-2 revealed a competitive inhibition. The SHP-2 expressing cells treated with MLS-001 demonstrated reduced SHP-2 phosphatase activity, thereby suggesting that MLS-001 effectively passes through cell membranes. In addition, MLS-001 reduced SHP-2-mediated phosphorylation in the activation loop of ERK in cells. Therefore, MLS-001 could be a lead compound for developing a potent SHP-2 inhibitor.