title: Endogenous erythroid colony formation in chronic myeloid leukemia: a recurrent finding associated with persistent minimal residual disease under imatinib.
abstract: In vitro endogenous erythroid colony (EEC) formation is a common finding in BCR-ABL-negative myeloproliferative neoplasms. The aim of the present study was to determine the prevalence and the clinical significance of EEC growth in chronic myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52 patients with newly diagnosed CML were correlated with disease characteristics at presentation and molecular response to imatinib. EECs (median 7 per dish, range 1-39) were detectable in 16 patients (31%). The proportion of patients with a high-risk Sokal score was lower in the EEC group (7% vs. 30%, respectively). The cumulative incidence of achieving a major molecular response after 2 years of imatinib was similar for both groups. However, patients with EECs were less likely to achieve a more profound decline of BCR-ABL transcripts. After 6 years of imatinib, the cumulative probability [95% CI] of reaching a ≥4 log reduction of BCR-ABL was 48% [16%; 92%] for patients of the EEC group and 84% [63%; 97%] for patients of the No EEC group. The probability [95% CI] of achieving a >4.5 log reduction of BCR-ABL after 7 years was 13% [2%; 61%] for patients with EECs and 52% [30%; 78%] for patients without EECs. In vitro EECs disappeared after achievement of a major molecular response in all evaluable patients. The data indicate that EEC formation is a recurrent finding in patients with CML which deserves further attention as a possible biomarker predicting the degree of molecular response to imatinib.
authors.affiliation: 1 Department of Laboratory Medicine, Medical University of Vienna , Vienna, Austria .
authors.forename: Elisa
authors.initials: E
authors.lastname: Einwallner
authors.forename: Eva
authors.initials: E
authors.lastname: Jaeger
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Mitterbauer-Hohendanner
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.forename: Ingrid
authors.initials: I
authors.lastname: Simonitsch-Klupp
authors.forename: Irene
authors.initials: I
authors.lastname: Steiner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pernicka
authors.forename: Gregor
authors.initials: G
authors.lastname: Hoermann
authors.forename: Susanne
authors.initials: S
authors.lastname: Herndlhofer
authors.forename: Christian
authors.initials: C
authors.lastname: Sillaber
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Ilse
authors.initials: I
authors.lastname: Schwarzinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D041905:Erythroid Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000150:complications* / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D050799:STAT5 Transcription Factor; D000068877:Imatinib Mesylate