Abstract

To investigate whether serum biomarkers can be used to indicate the responsiveness of acute myeloid leukemia to remission induction chemotherapy, we performed MALDI-TOF protein profile analysis of patient sera. The resulting spectra revealed a protein (or peptide) peak at m/z 7764 that varied in intensity; its intensity was much higher in samples from patients in complete remission than in those from patients with resistant disease or in samples taken prior to treatment (at the time of diagnosis). Using fractionation, trypsin digestion, MS/MS, and protein molecular weight analyses, we identified the m/z 7764 protein as platelet factor-4 (PF4). This identification was confirmed by a magnetic bead-based MALDI immunoassay. Statistical comparison of PF4 levels and platelet counts in patient sera revealed a significant positive correlation between the two variables. This study demonstrates that PF4 protein levels are a good indicator for the recovery of blood count in the complete remission of acute myeloid leukemia. The linear positive correlation curve indicates that blood count recovery of platelets to >100,000/mm(3) is equivalent to a serum PF4 recovery level of >2.492 microg/ml.

Highlights

  • To investigate whether serum biomarkers can be used to indicate the responsiveness of acute myeloid leukemia to remission induction chemotherapy, we performed MALDI-TOF protein profile analysis of patient sera

  • Our results demonstrate that MALDI-TOF protein profile analysis of bone marrow sera of acute myeloid leukemias (AMLs) patients after complete remission (CR) induction chemotherapy can differentiate between CR and resistant disease (RD) states

  • odds ratio (OR) for the risk of being a CR responder is computed for an increase of 1 unit of ⌬7764.8 level

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Summary

Introduction

To investigate whether serum biomarkers can be used to indicate the responsiveness of acute myeloid leukemia to remission induction chemotherapy, we performed MALDI-TOF protein profile analysis of patient sera. The curability of AML is influenced by many pretreatment factors, including patient age, chromosome abnormality, previous hematological disorder, presenting leukocyte count, and leukemic cell characteristics. In addition to these variables, several treatment factors correlate with prognosis in AML including, most importantly, achievement of complete remission (CR) [1]. All-trans-retinoic acid (ATRA) is used only for remission induction of a subtype (M3) of AML After induction chemotherapy, both bone marrow and blood are examined to determine whether the leukemia has been eliminated

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