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

Rasche, Leo; Angtuaco, Edgardo; McDonald, James E.; Buros, Amy; Stein, Caleb; Pawlyn, Charlotte; Thanendrarajan, Sharmilan; Schinke, Carolina; Samant, Rohan and Yaccoby, Shmuel, et al. (2017) In Blood 130(1). p.30-34
Abstract

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... (More)

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.

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published
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Blood
volume
130
issue
1
pages
5 pages
publisher
American Society of Hematology
external identifiers
  • scopus:85024106403
  • wos:000404856900009
ISSN
0006-4971
DOI
10.1182/blood-2017-03-774422
language
English
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yes
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ba4bb929-420e-40e0-989b-ff1e1d88c6b3
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2017-08-03 10:48:23
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2017-09-18 11:40:52
@article{ba4bb929-420e-40e0-989b-ff1e1d88c6b3,
  abstract     = {<p> <sup>18</sup>F-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 &lt; .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.</p>},
  author       = {Rasche, Leo and Angtuaco, Edgardo and McDonald, James E. and Buros, Amy and Stein, Caleb and Pawlyn, Charlotte and Thanendrarajan, Sharmilan and Schinke, Carolina and Samant, Rohan and Yaccoby, Shmuel and Walker, Brian A. and Epstein, Joshua and Zangari, Maurizio and Van Rhee, Frits and Meissner, Tobias and Goldschmidt, Hartmut and Hemminki, Kari and Houlston, Richard and Barlogie, Bart and Davies, Faith E. and Morgan, Gareth J. and Weinhold, Niels},
  issn         = {0006-4971},
  language     = {eng},
  month        = {07},
  number       = {1},
  pages        = {30--34},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Low expression of hexokinase-2 is associated with false-negative FDG–positron emission tomography in multiple myeloma},
  url          = {http://dx.doi.org/10.1182/blood-2017-03-774422},
  volume       = {130},
  year         = {2017},
}