Hypermethylation of calcitonin gene in adult acute leukemia at diagnosis and during complete remission

Hypermethylation of the calcitonin gene has been described in various hemat ologic malignancies. In order to assess its frequency and potential usefuln ess as a marker for leukemic cells and to detect potential clinical correla tions, 180 adult patients (aged > 15 years) with newly diagnosed acute leuk emia including 133 cases of acute myeloid leukemia (AML) and 47 cases of ac ute lymphoblastic leukemia (ALL) were tested for its presence in leukemic b lasts at diagnosis by Southern blot technique and polymerase chain reaction (PCR) using 3 sets of primers (P550, P566, P1400), amplifying the most fre quent sites of hypermethylation upstream or within the gene. In AML, 92 pat ients (69%) had hypermethylation detected by Southern blot at diagnosis. Th is hypermethylation could be confirmed by PCR in 18 of 36 tested cases (50% ). Hypermethylation was not significantly associated to any clinical or hem atological characteristic of the disease. In ALL, 44 patients (94%) had hyp ermethylation detected by Southern blot at diagnosis. This hypermethylation could be confirmed by PCR in 33 of the 43 tested cases (77%). Sensitivity of PCR assessed by dilution was 1 to 0.1%. Hypermethylation was not either significantly related to any clinical or hematologic characteristics of the disease. Seven ALL cases which were positive by PCR at diagnosis and achie ved cytological CR could be tested during CR. Five cases were negative and did not relapse after 3 to 27 months in CR. One case was positive at the be ginning of CR and became negative after autologous transplant. However, he relapsed after 9 months in CR, 3 months after the last negative test. PCR f or Bcr/Abl was also negative at this time. We conclude that hypermethylatio n of the calcitonine gene is frequent at diagnosis in adult acute leukemia, particularly in ALL.