Combiation Of Interphase- And Metaphase- Fluorescent In Situ Hybridization To Identify 11q23/MLL Gene Arrangements In Adult Patients With Acute Leukemia

ObjectiveAcute leukemia (AL) with 11q23/MLL gene arrangements is a recurrent cytogenetic abnormality. AL patiemts with 11q23/MLL gene arrangements are often associated with early relapse and poor prognosis. Because of the numerous partners of the translocations and the various types of the arrangements involving 11q23/MLL, it is difficult for conventional cytogenetic assay (CCA) to disclose all MLL arrangements. Thus it is critical to employ a rapid, sensitive and efficient test to investigate the incidence and clinical characteristics of AL patients with 11q23/MLL gene arrangements, which is helpful for risk-based treatment of AL.MethodBone marrow samples of 112 adult AL patients were collected at presentation, prepared by short-term (24 hours) unstimulated culture, and karyotyped by R-banding. The abnormal signals were screened by interphase- fluorescence in situ hybridization (FISH) with dual-color breakapart 11q23/MLL -specific probe, and the 11q23/MLL gene rearrangements were determined by metaphase- FISH.Result:Of the 112 patients, 9 patients (8.0%) with 11q23/MLL translocations were revealed by FISH, compared with that of 4 patients (3.6%) by CCA. Of three patients with del(11)(q23) reported by CCA, FISH showed two were 11q23/MLL translocations and one was true deletion of 11q23 telemoric terminal, 11q23/MLL translocations were also identified by FISH in one patient with normal karyotype, one patient with 11q+ and one patient without overt 11q23 abnormality. Aside from the 9 patients with 11q23/MLL translocations, 8 patients with MLL gene amplification including polysome, homogenous staining region (hsr), segmental jumping translocation (SJT) and double minute chromosome (dmin) were disclosed by FISH. AL patients with 11q23/MLL abnormalities were frequently diagnosed as pro-B acute lymphoblastic leukemia (pro-B ALL), acute monocytic leukemia (AMoL) or biphenotypic acute leukemia (BAL). Myelodysplasis in ALL patients is more obvious than in AML patients. High expression of CD34 were observed in ALL patients 11q23/MLL abnormaliy, while high expression of CD117, CD56 and CD64 were observed in AML patients 11q23/MLL abnormaliy.ConclusionFISH with dual-color breakapart 11q23/MLL -specific probe is rapid and sensitive method to facilitate the detection of 11q23/MLL abnormalities. The incidence of 11q23/MLL abnormalities detected by FISH is much higher than that by CCA. FISH effectively discloses translocations and amplifications involving 11q23/MLL, and should be performed to identify 11q23/MLL abnormalities in patients diagnosed as pro-B ALL, AMoL or BAL, especially with normal karyotype.