DELETION OF THE SHORT ARM OF CHROMOSOME-12 IS A SECONDARY EVENT IN ACUTE LYMPHOBLASTIC-LEUKEMIA WITH T(12-21)

Translocation t(12;21) has been described as a nonrandom event in acut e lymphoblastic leukemia (ALL) in patients with deletion of the short arm of chromosome 12, using fluorescence in site hybridization techniq ues. Extensive FISH experiments were performed in order to re-examine the short arm of chromosome 12 in three children with ALL, previously shown to have t(12;21). It was shown that the t(12;21) is undetectable by routine R-banding technique and that the translocated 12 looks lik e a cytogenetically normal chromosome 12 in the three patients. Partia l 12p deletion involving the TEL locus was shown to be interstitial in one patient with 12p- by using cosmid and YAC probes. In the second p atient, the 12p- chromosome was secondary to the translocation since i t was observed in about one half of the metaphases analyzed with FISH. In the third patient, the region of TEL usually rearranged in the t(1 2;21) displayed a germline pattern by Southern blotting, at diagnosis and in relapse. A few metaphases showed associated 12p- by standard cy togenetics, only in relapse. Thus, we conclude that the TEL allele not involved in t(12;21) is inconstantly lost in patients with this subty pe of ALL and occurs on the 12p- chromosome. These data question the s tatus of tumor suppressor gene hypothesized for TEL.