Biomarker analysis in polycythemia vera under interferon-alpha treatment: clonality, EEC, PRV-1, and JAK2 V617F.
Three consecutive polycythemia vera (PV) patients were analyzed before and during pegylated-interferon (rIFNalpha) treatment for the following markers: (1) granulocyte and CD34(+) cell clonality, (2) Jak2V617F expression, (3) PRV-1 mRNA overexpression, and (4) Epo-independent colony (EEC) growth. Before rIFNalpha therapy, all patients displayed clonal hematopoiesis, 100% Jak2V617F expression as well as PRV-1 overexpression, and EEC growth. After rIFNalpha treatment, all three patients demonstrated polyclonal hematopoiesis. Nonetheless, Jak2V617F expression, PRV-1 overexpression, and EEC-growth remained detectable, albeit at lower levels. We conclude that reemergence of polyclonal hematopoiesis after rIFNalpha treatment may be achieved in a substantial proportion of patients. However, this does not constitute elimination of the PV clone. These data demonstrate the usefulness of novel markers in monitoring minimal residual disease and caution against discontinuation of rIFNalpha treatment after hematologic remission. Long-term follow-up of large patient cohorts is required to determine whether rIFNalpha treatment can cause complete molecular remissions in PV.
Steimle
C
C
Department of Experimental Anaesthesiology, University Hospital Freiburg, Center for Clinical Research, Freiburg, Germany.
Lehmann
U
U
Temerinac
S
S
Goerttler
Ph S
PS
Kreipe
H
H
Meinhardt
G
G
Heimpel
H
H
Pahl
H L
HL
D000328:Adult; D019943:Amino Acid Substitution; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D058851:GPI-Linked Proteins; D015870:Gene Expression / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use*; D007519:Isoantigens / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D018952:Antigens, CD34; D015415:Biomarkers; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D016898:Interferon-alpha; D007519:Isoantigens; D008562:Membrane Glycoproteins; D050505:Mutant Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004921:Erythropoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2