A 14-year-old girl was admitted to the Department of Pediatric Hematology, Oncology, and Transplantology, Medical University of Lublin in Poland due to an anemia and weakness. Lymphadenopathy, hepatosplenomegaly, and the infiltration of the central nervous system were not found. The laboratory results were as follows: white blood cell (WBC) 1,950/microL, platelet count 120,000/microL, and hemoglobin level 10.8 g/dL. Evaluation of the bone marrow showed 73% blast cells. The girl was diagnosed with preB common positive ALL in May 2018 and she was treated according to the ALL Intercontinental-Berlin-Frankfurt-Munster 2009 (ALL IC-BFM 2009) protocol for the intermediate risk group.
Cytogenetic analysis was performed on a bone marrow sample. G-banded chromosome analysis revealed a female karyotype 47,XX,+mar/46,XX. Poor quality of the metaphase chromosomes made them impossible to evaluate. FISH was performed with use of the commercially available probes: BCR/ABL1, KMT2A, ETV6/RUNX1 (Vysis, Abbott Molecular, Des Plaines, IL, USA). No rearrangements were found in BCR/ABL1, KMT2A, or ETV6/RUNX1 tests. FISH analysis revealed between 6 and 9 signals of RUNX1 in 80.6% of the analyzed nuclei. Metaphases showed that extra signals were clustered together and located on abnormal chromosomes difficult to identify (Fig. 1A). CytoScan HD array (Thermo Fisher Scientific, Waltham, MA, USA) was performed on the same sample of bone marrow. This method confirmed iAMP21 arr[GRCh37] 21q21.3q22.3(28054448_43559902)x4. The size of amplification was 15.5 Mb and contained the following genes: DYRK1A, TMPRSS2, OLIG2, RUNX1, ADAMTS1, TIAM1, ETS2, and ERG. Apart from this, analysis revealed duplication of a fragment of the long arm of chromosome 1, deletion within 4-7 exons of the IKZF1 gene, deletion within chromosome 13 including the RB1 gene (20-27 exon biallelic deletion), and deletion of band 21q22.3 (PTTG1IP, S100B, TFF3, U2AF1, TMPRSS3, TFF1, TFF2, CSTB). Loss of heterozygosity of the entire chromosome 22 was also demonstrated (Fig. 1B). FISH analysis revealed that additional signals were located on a large, hard to identify chromosome. Microarray analysis suggested translocation between chromosome 21 and a fragment of the long arm of chromosome 1. Performing a FISH test with whole chromosome painting probes for chromosomes 1 and 21 (Cytocell Ltd, Oxford Gene Technology, Cambridge, UK) confirmed translocation. Additional RUNX1 signals were clustered together on this translocated chromosome.