Sequential fluorescence in situ hybridization analyses for trisomy 12 in chronic leukemic B-cell disorders.
OBJECTIVE
Trisomy 12 is one of the most common chromosomal abnormalities in B-cell chronic lymphocytic leukemia (CLL). The aberration is readily detected by fluorescence in situ hybridization (FISH). There are only a few reports in which FISH analyses have been used to study the expansion of the trisomy 12 clone over time.


METHODS
Repeat FISH analyses were performed in 77 patients with a chronic leukemic B-cell disorder. The aim was to study the development of the trisomy 12 clone throughout the course of the disease, to measure the effect of therapy on the proportion of trisomic cells, and to relate the findings to the response to therapy.


RESULTS
Fifty-eight of the 60 patients with no trisomy 12 at the initial test were consistently disomic for chromosome 12, while 2 patients seemingly acquired trisomy 12 during follow-up. Seventeen patients showed trisomy 12 at the first test. Expansion of the trisomy 12 clone was seen in all patients with a progressive lymphocytosis. In contrast to poor responders, patients responding well to chemotherapy showed a significant decrease in the proportion of CD19+ cells with trisomy 12. The effect of purine analogs in patients with trisomy 12 seemed inferior, both clinically and when studying the effect on the trisomic clone.


CONCLUSIONS
There is a strong association between expansion of the trisomy 12 clone and progressive disease, both in treated and untreated patients. Conversely, reduction of the trisomic B-cell clone was linked to clinical response to chemotherapy. Acquisition of trisomy 12 remains a rare event.
Division of Hematology, Karolinska Hospital, SE-171 76 Stockholm, Sweden. viktoria.hjalmar@kids.ki.se
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Hjalmar
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Hast
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Kimby
D000970:Antineoplastic Agents / Q000008:administration & dosage; D002881:Chromosomes, Human, Pair 12 / Q000187:drug effects / Q000235:genetics*; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D011446:Prospective Studies; D014314:Trisomy / Q000175:diagnosis*
D000970:Antineoplastic Agents