Cellular increase in the heat shock protein 70 (HSP70) inhibits death receptor and mitochondria-initiated signaling for apoptosis. In Vitro and in vivo data from patients with chronic myeloid leukemia (CML) indicates that overexpression of HSP70 in leukemic cells is associated with resistance to imatinib. The HSP70 protein is detectable in the plasma and has been reported to represent a marker for cardiovascular stress as well as prostate cancer. We measured HSP70 in the plasma of 139 patients with CML using a sandwich assay based on meso scale technology and correlated levels of HSP70 protein in plasma with clinical behavior. All samples were collected prior to initiating imatinib therapy. The levels of HSP70 in CML patients in chronic phase (N=93) were not significantly (P=0.08) different from those in patients with CML in accelerated/blast crisis (N=46) (median 33.24 ng/ml, range: 3.892–128.172 ng/ml Vs median 26.57 ng/ml, range: 4.498–114.746 ng/ml, respectively). However, CML patients had significantly (P<0.0001) higher levels of HSP70 than normal control (N=95, median=4.17 ng/ml, range:1.746–24.684 ng/ml). There was significant correlation between plasma levels of HSP70 and platelets (r=0.54), WBC (r=0.32), and basophils (r=0.31) in patients in chronic phase and with platelets (r=0.72), blasts (r=0.39), and basophils (r=0.50) in patients in Acc/Bl phase. Patients in chronic phase and high levels above the median had significantly (P=0.02) higher rate of progression to ACC/Bl phase while on therapy with imatinib (figure). In addition these patients appear to have a tendency toward shorter survival (P=0.07). There was no significant correlation between plasma HSP70 levels and survival in patients with ACC/Bl phase. This data support the reported role of HSP70 in the resistance to imatinib in patients with CML and potentially plasma HSP70 levels may represent a marker for resistance in patients with chronic phase CML.

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Topics:
heat-shock proteins 70, imatinib mesylate, leukemia, myelocytic, chronic, blast phase, death domain receptors, leukemia, myeloid, chronic-phase, leukemic cells, prostate cancer, stress, basophils

Author notes

Disclosure: No relevant conflicts of interest to declare.

2007, The American Society of Hematology
2007
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