Low expression of hexokinase-2 is associated with false-negative FDG–positron emission tomography in multiple myeloma

Leo Rasche, Edgardo Angtuaco, James E. McDonald, Amy Buros, Caleb Stein, Charlotte Pawlyn, Sharmilan Thanendrarajan, Carolina Schinke, Rohan Samant, Shmuel Yaccoby, Brian A. Walker, Joshua Epstein, Maurizio Zangari, Frits van Rhee, Tobias Meissner, Hartmut Goldschmidt, Kari Hemminki, Richard Houlston, Bart Barlogie, Faith E. Davies, Gareth J. Morgan and Niels Weinhold

Key Points

  • PET false-negativity was seen in 11% of MM patients.

  • PET false-negativity was associated with low hexokinase-2 expression.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.


18F-Fluorodeoxyglucose (FDG)–positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging with background signal suppression (DWIBS) are 2 powerful functional imaging modalities in the evaluation of malignant plasma cell (PC) disease multiple myeloma (MM). Preliminary observations have suggested that MM patients with extensive disease according to DWIBS may be reported as being disease-free on FDG-PET (“PET false-negative”). The aim of this study was to describe the proportion of PET false-negativity in a representative set of 227 newly diagnosed MM patients with simultaneous assessment of FDG-PET and DWIBS, and to identify tumor-intrinsic features associated with this pattern. We found the incidence of PET false-negativity to be 11%. Neither tumor load–associated parameters, such as degree of bone marrow PC infiltration, nor the PC proliferation rate were associated with this subset. However, the gene coding for hexokinase-2, which catalyzes the first step of glycolysis, was significantly lower expressed in PET false-negative cases (5.3-fold change, P < .001) which provides a mechanistic explanation for this feature. In conclusion, we demonstrate a relevant number of patients with FDG-PET false-negative MM and a strong association between hexokinase-2 expression and this negativity: a finding which may also be relevant for clinical imaging of other hematological cancers.

  • Submitted March 22, 2017.
  • Accepted April 13, 2017.
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