CLONAL INSTABILITY PRECEDING LYMPHOID BLASTIC TRANSFORMATION OF CHRONIC MYELOID-LEUKEMIA

Citation
A. Spencer et al., CLONAL INSTABILITY PRECEDING LYMPHOID BLASTIC TRANSFORMATION OF CHRONIC MYELOID-LEUKEMIA, Leukemia, 11(2), 1997, pp. 195-201
Citations number
29
Categorie Soggetti
Hematology,Oncology
Journal title
ISSN journal
08876924
Volume
11
Issue
2
Year of publication
1997
Pages
195 - 201
Database
ISI
SICI code
0887-6924(1997)11:2<195:CIPLBT>2.0.ZU;2-X
Abstract
We have sought the presence of rearrangements of the immunoglobulin he avy chain gene locus in 13 patients with chronic myeloid leukemia (CML ) in lymphoid blastic transformation (L-BT) using the polymerase chain reaction (PCR). The lymphoid nature of the transformation was confirm ed by immunophenotyping and/or Southern blot hybridization with a J(H) probe. Clonal rearrangements were detected in 85% of cases and two or more rearrangements were visible in 64% of informative cases. The pat tern of V-H gene family utilization revealed an apparent reduction in V-H 4 family gene usage but otherwise reflected the known proportion o f each gene family in the germline repertoire. In six cases the third complementary determining regions (CDR3) of the predominant blast cris is clone/s were sequenced revealing minimal evidence of somatic mutati on. No clonal changes were detected in the chronic phase leukemia cell s collected more than 6 months before the onset of L-BT in three of th ese patients. Of the other three patients studied in chronic phase fro m 1 to 6 months before L-BT, two showed clonal rearrangements which di ffered in size from those present at L-BT. In one patient a V(H)3 to V (H)5-D-H-J(H) substitution had occurred at least 3 months prior to L-B T. In the other patient, however, the sequence of the rearrangement pr esent 5 months prior to L-BT was unrelated to the rearrangements at th e time of L-BT indicating a pattern of clonal succession. We conclude that: (1) IgH gene rearrangements are detectable in the majority of pa tients with L-BT using PCR and the lymphoid lineage of blastic CML is most readily confirmed using consensus primers to the framework 3 regi on; (2) somatic mutation is uncommon; and (3)B lymphoid clones distinc t from those identified later may be detected before overt lymphoid BT . The identification of such 'abortive' clones is evidence for clonal instability before the onset of transformation and might have prognost ic value.