Table 2.
Clinical significance of HMGB1 and RAGE in hematologic malignancies
| Study | Neoplasm | Assay | Clinical significance |
|---|---|---|---|
| Court et al. (2004) | AML | cDNA microarray, real-time PCR, Southern blot | AML patient samples exhibited significantly higher expression of HMGB1 than controls (p = 0.009) |
| Xu et al. (2004) | ALL | qRT-PCR, Western blot | HMGB1 mRNA and protein levels were increased in ALL specimens when compared to normal lymphocytes |
| Meyer et al. (2008) | NHL | qRT-PCR, IHC | HMGB1 level was higher in 11/18 lymphoma samples, compared with the average of the controls In positive samples, HMGB1 was localized to the nucleus and specifically in lymphoma cells, not surrounding cells |
| Zappasodi et al. (2010) | NHL | ELISA | HMGB1 release from treated tumor cells did not statistically differ by treatment (doxorubicin, UVC, γ irradiation, and HS, single or combined), suggesting much variation in ability to emit immunogenic signaling in lymphoma cells |
| Nomura et al. (2011) | Variousa | ELISA | Patients with DIC associated with hematologic malignancy exhibited a decrease in serum HMGB1 after rTM therapy (p < 0.001) HMGB1 correlated with other serum markers including prothrombin time, fibrinogen, C-reactive protein, IL-6, and TNF-α (all, p < 0.05) |
| Mao et al. (2012) | T cell lymphoma | IHC | HMGB1 was present in the cytosol in 72% (n = 65) lymphoma cases vs. 45% (n = 18/40) of reactive lymphoid hyperplasia controls (p < 0.05) Overexpression of HMGB1 was associated with tumor aggressiveness (p < 0.001) and clinical stage (p < 0.001) |
| Inoue et al. (2013) | Variousb | ELISA | NSD in serum HMGB1 between patients in complete remission vs. refractory malignancy Malignancy complicated by SIRS had significantly higher serum HMGB1 compared with patients in remission (p = 0.001) or with refractory malignancy (p = 0.08) Resolution of SIRS (n = 13) led to decreased serum HMGB1 High HMGB1 in SIRS cancer patients was associated with early death within 1 month (p = 0.016) |
| Jia et al. (2014) | CLL | Plasma: ELISA LN: TMA, IHC |
Plasma HMGB1 levels correlated with acute lymphocyte count (p < 0.0001) Decreased LN HMGB1 overall (p < 0.0001), but increased cytoplasmic expression Increased HMGB1-containing cells in LN was associated with shorter overall survival (p = 0.03) RAGE is strongly expressed in LN of patients with CLL |
| Kimura et al. (2014) | ATLL | ELISA | HMGB1 tended to be higher in ATLL plasma than healthy controls (p = 0.051) |
| Lu et al. (2014) | AML | qRT-PCR, Western blot | Increased HMGB1 expression in relapsed/refractory AML patients compared to newly diagnosed patients (p < 0.05) |
DLBCL (n = 8), anaplastic large T cell lymphoma (n = 1), follicular lymphoma (n = 6), small lymphocytic lymphoma (n = 2), nodal marginal zone BCL (n = 1)
AML (n = 18), ALL (n = 5), DLBCL (n = 7), follicular lymphoma (n = 5), angioimmunoblastic T cell lymphoma (n = 1), myelodysplastic syndrome (n = 8), multiple myeloma (n = 5), adult ATLL (n = 1), complicated hematopoietic stem cell transplant patient (n = 4).
ALL – acute lymphocytic leukemia; AML – acute myeloid leukemia; ATLL – acute T cell lymphocytic leukemia; BCL – B cell lymphoma; CLL – chronic lymphocytic leukemia; DLBCL – diffuse large B cell lymphoma; NHL – non-Hodgkin lymphoma; NSD – no significant difference; qRT-PCR – quantitative real-time polymerase chain reaction; rTM – recombinant thrombomodulin; SIRS – systemic inflammatory response syndrome; TMA – tissue microarray