Clonality analysis as a tool to study the biology and response to therapy in myelodysplastic syndromes.
We examined the bone marrow of 45 patients with MDS at the time of diagnosis and in the course of the disease by means of Southern blot analysis and cytogenetic studies to detect and evaluate clonal markers and their implication on the prognosis of the disease and the response to treatment. All patients were enrolled in an EORTC study and received low-dose Ara-C with or without growth factors according to the study protocol. Thirty patients (67%) were characterized by different clonal markers, such as various gene rearrangements (eg Ig-JH, tcR-beta, bcr, GM-CSF, G-CSF or IL-3) and/or chromosomal markers at the time of diagnosis or early in the course of the disease. In 23 of 30 cases that could be studied in the course of the disease, a statement about the clonal situation was possible: in three cases (8%) the clonal situation did not change, in nine cases (39%) at least a transient reduction of clonal cells could be demonstrated, suggesting partial or complete response to therapy. In eight cases (35%) a change for the worse could be seen. In four cases (17%) involvement of multiple clones could be demonstrated with the clones exhibiting different susceptibilities to treatment. Clinical evaluation showed that patients without clonal markers at diagnosis had a better prognosis as compared to patients who presented with clonal markers. We suggest that clonality analysis at diagnosis and in the course of the disease will be a useful tool to study the biology and response to treatment in MDS.
Schmetzer
H M
HM
Klinikum Grosshadern, University of Munich, Germany.
Poleck
B
B
Mittermüller
J
J
Duell
T
T
Wilmanns
W
W
Gerhartz
H H
HH
D015139:Blotting, Southern; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D005819:Genetic Markers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011336:Probability; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D013997:Time Factors
D005819:Genetic Markers; D011994:Recombinant Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor