Screening by fluorescence in situ hybridization for MLL status at diagnosis in 239 unselected patients with acute myeloblastic leukemia

A large number of abnormalities involving the MLL gene have been associated with hematological malignancies, including acute myeloblastic leukemias (AML). Given the overall unfavorable prognosis of AML with an MLL abnormality, its reliable and accurate detection is needed for informed treatment decision. We therefore investigated the occurrence of MLL abnormalities in 239 unselected consecutive AML patients, using conventional cytogenetic and fluorescent in situ hybridization (FISH) analyses. FISH analysis for MLL was performed using a commercial dual-color probe. Of the 239 patients, 30 (12.6%) showed MLL abnormalities under FISH analysis, 10 (4.2%) showed a split signal indicating the disruption of the MLL gene by translocation or insertion, and 20 (8.4%) showed overrepresentation of the MLL gene without evidence of rearrangement. MLL abnormalities were more frequently found in AML-M5 and M4, mainly as rearrangements, and in AML-M2, mainly as overrepresentation. Our results are in agreement with those reported in other studies. All M2, M4, and M5 AML patients without known recurrent translocations, such as t(8;21) and inv(16), should be investigated by FISH with an MLL probe because it allows the detection of MLL rearrangement that would go undetected by conventional cytogenetics and because it has the ability of detecting multiple copies of the MLL gene in, for example, marker chromosomes and double minutes.