Cryptic ins(4;11)(q21;q23q23): a variant of t(4;11)(q21;q23) in an infant with an immature B-ALL. C.A. Tirado¹, A.M. Meloni-Ehrig¹, T. Edwards¹, J. Scheerle¹, K. Burks¹, C. Repetti², J.C. Kelly¹, N.C. Christacos¹, J. Grenberg³, C.D. Croft¹, D. Heritage¹, P.N. Mowrey¹. 1) Cytogenetics, Quest Diagnostics Nichols Institute, Chantilly, VA 20151; 2) Flow Cytometry, Quest Diagnostics Nichols Institute, Chantilly, VA 20151; 3) Arlington-Fairfax Hematology-Oncology, Arlington, VA.
   We report on a 4-year-old female with a WBC of 120,000 and thrombocytopenia. The blood findings revealed a Hb of 10 g/dL, a hematocrit of 29%, and a platelet count of 47 K/L. The flow cytometry report identified abnormal blasts which were CD10-, CD19+, partial dim TdT, HLA-DR +, and CD15+ consistent with an immature B-cell lineage acute lymphoblastic leukemia. Routine chromosome analysis detected an isochromosome 7q resulting in loss of the short arm and gain of the long arm of chromosome 7, as well as a possible loss of material from 11q23. FISH studies on both interphase nuclei and metaphase cells using the LSI MLL Dual Color, Break Apart Rearrangement probe (Abbott Molecular, Inc.) were instrumental in the characterization of an MLL gene rearrangement, which was cryptic by conventional cytogenetic analysis. Specifically, the FISH pattern was consistent with an insertion of the 5' region of the MLL gene into one chromosome 4 at band q21. Insertions of the MLL gene into various partner chromosomes have been reported previously. To our knowledge, this particular insertion of the MLL gene into chromosome 4 has only been reported once. We assume that this cryptic insertion results in the fusion of the 5' portion of the MLL gene with the AF4 gene at 4q21, as is seen in the typical t(4;11)(q21;q23). This translocation has been reported mostly in very young children (1-2 years of age, 50% are under 4 years ), as well as adults and it is usually associated with an unfavorable prognosis. The presence of the i(7q), which is an additional abnormality seen in approximately 10% of ALL cases with t(4;11)(q21;q23), strengthens the possibility that this insertion is a variant of the typical t(4;11)(q21;q23). This case exemplifies the importance of FISH in the further characterization of cytogenetic abnormalities in hematologic oncology cases.