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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2001-11-0142.
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Blood, 15 June 2003, Vol. 101, No. 12, pp. 4937-4943
NEOPLASIA
Jak1 deficiency leads to enhanced Abelson-induced B-cell tumor formation
Veronika Sexl,
Boris Kovacic,
Roland Piekorz,
Richard Moriggl,
Dagmar Stoiber,
Angelika Hoffmeyer,
Rita Liebminger,
Oliver Kudlacek,
Eva Weisz,
Kristen Rothammer, and
James N. Ihle
From the Department of Pharmacology, Vienna University, Austria; and Howard Hughes Medical Institute, Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN.
The Janus kinase Jak1 has been implicated in tumor formation by the Abelson oncogene. In this study we show that loss of Jak1 does not affect in vitro transformation by v-abl as defined by the ability to induce cytokine-independent B-cell colony formation or establishment of B-cell lines. However, Jak1-deficient, v-abl–transformed cell lines were more tumorgenic than wild-type cells when transplanted subcutaneously into severe combined immunodeficient (SCID) mice or injected intravenously into nude mice. Jak1 deficiency was associated with a loss in the ability of interferon- (IFN-)to induce growth arrest and/or apoptosis of v-abl–transformed pre-B cells or tumor growth in SCID mice. Moreover, IFN- mRNA could be detected in growing tumors, and tumor cells explanted from SCID mice had lost the ability to respond to IFN- in 9 of 20 cases, whereas the response to interferon- (IFN-) remained intact. Importantly, a similar increase in tumorgenicity was observed when IFN-–deficient cells were injected into SCID mice, identifying the tumor cell itself as the main source of IFN-. These findings demonstrate that Jak1, rather than promoting tumorgenesis as previously proposed, is critical in mediating an intrinsic IFN-–dependent tumor surveillance.
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