A complex 1;19;11 translocation involving the MLL gene in a patient with congenital acute monoblastic leukemia identified by molecular and cytogenetic techniques

Abstract

Dear Editor, Translocations involving chromosomal band 11q23 are found in most of the infant acute lymphoblastic leukemia and in acute myeloblastic leukemia. The majority of these translocations lead to the rearrangement of the MLL gene and the formation of new chimeric genes [1]. We report here a case of congenital acute monoblastic leukemia and myeloid sarcoma associated with an apparent t(1;11)(p36; q23) which proved to be in fact a complex 1;19;11 translocation. This female child was born after a pregnancy of 33 weeks and 6 days complicated by gravidic toxemia and hydramnios. At birth, the baby was cyanosed and showed no reaction to stimuli. She had disseminated intravascular coagulation with petechiae and hematoma on the neck and the limbs. Cutaneous tumors were observed on the abdomen, the right arm and the left thigh. Her hematological data were as follows: hemoglobin 14 g/dl, white blood cells (WBC) 162×10/L with 0.5% neutrophils, 0.5% eosinophils, 9.5% lymphocytes, 8% monocytes and 80% monoblasts and promonocytes, and platelets 50×10/L. A diagnosis of acute monoblastic leukemia (FAB type M5) was made. The biopsy of one cutaneous tumor showed a massive derma infiltration by monoblasts; therefore, these skin tumors were considered to be myeloid sarcomas. Palliative care solely was applied. The child developed acute renal insufficiency and massive cerebral hemorrhage, of which she died 24 h after birth [2]. Cytogenetic analysis was performed on bone marrow cells with standard techniques. We observed a translocation which appeared to be balanced in R-banding between chromosomes 1 and 11; thus, the karyotype was written as 46,XX,t(1;11)(p36.2;q23). FISH analysis using the LSI MLL dual color probe (Abbott, Rungis, France) confirmed the disruption of the MLL gene. It showed the translocation of the 3′ region of MLL (red signal) to the derivative chromosome 1 while the 5′ region (green signal) remained on the der(11). We then used long-distance inverse PCR (LDI-PCR) to identify the MLL fusion partner involved in the chromosomal translocation of that particular patient [3]. Genomic DNA was isolated from methanol/acetic acid-fixed cells of leukemia patient that were stored at −20°C. DNA was extracted using the QIAamp DNA mini kit (Qiagen GmbH, Hilden, Germany) according to the manufacturer recommendations. After DNA digestion, resulting DNA fragments were re-ligated to form DNA circles prior to LDIPCR studies. LDI-PCR reactions were performed as Ann Hematol (2009) 88:795–797 DOI 10.1007/s00277-008-0656-8