SOUTHERN TECHNIQUE AND CYTOGENETICS ARE COMPLEMENTARY AND MUST BE USED TOGETHER IN THE EVALUATION OF PH1, M-BCR POSITIVE CHRONIC MYELOID-LEUKEMIA (CML) PATIENTS TREATED WITH ALPHA-INTERFERON (IFN-ALPHA)

Cytogenetic analysis is the gold standard for the follow-up of CML pat ients. The sensitivity of cytogenetics is fairly similar to that of So uthern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yiel d of metaphases. IFN alpha treatment can induce lack of growth of hemo poietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and compleme ntarity between analysis of karyotype and detection of M-BCR rearrange ment of Southern blot, We studied 43 Ph1 positive, M-BCR positive pre- BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Sou thern technique was performed onto DNA from peripheral blood leukocyte s treated with BgIII (and Xbal if necessary) and hybridized with the u niversal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highl y significant association between both tests was obtained, Of 48 sampl es analyzed, 34 were evaluable by both methods and 28 gave the same re sult for both tests, The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetic s; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response, All of the specimens not evaluable b y karyotyping were evaluable by Southern, One sample was not analyzabl e by Southern but it was evaluable by cytogenetic analysis, The inform ation obtained by Southern technique was clinically relevant, and deci sions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they a re not interchangeable. Cytogenetic and molecular studies are compleme ntary and must be employed together in CML patients treated with alpha -interferon. (C) 1996 Wiley-Liss, Inc.