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 patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement 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. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.
Steegmann
J L
JL
Hematology Department, Hospital de la Princesa, Madrid, Spain.
Requena
M J
MJ
Casado
L F
LF
Pico
M
M
Peñarrubia
M J
MJ
Ferro
M T
MT
Resino
M
M
Fernandez-Rañada
J M
JM
D015139:Blotting, Southern; D001856:Bone Marrow Examination; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis*; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D012074:Remission Induction; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016044:Fusion Proteins, bcr-abl