Panagopoulos Ioannis, Gorunova Ludmila, Kerndrup Gitte, Spetalen Signe, Tierens Anne, Osnes Liv T N, Andersen Kristin, Müller Lil-Sofie Ording, Hellebostad Marit, Zeller Bernward, Heim Sverre
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Nydalen, P.O.Box 4953, 0424 Oslo, Norway ; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Exp Hematol Oncol. 2016 Mar 5;5:8. doi: 10.1186/s40164-016-0037-2. eCollection 2015.
The chromosomal translocation t(11;19)(q23;p13) with a breakpoint within subband 19p13.1 is found mainly in acute myeloid leukemia (AML) and results in the MLL-ELL fusion gene. Variations in the structure of MLL-ELL seem to influence the leukemogenic potency of the fusion in vivo and may lie behind differences in clinical features. The number of cases reported so far is very limited and the addition of more information about MLL-ELL variants is essential if the possible clinical significance of rare fusions is to be determined.
Cytogenetic and molecular genetic analyses were done on the bone marrow cells of a 20-month-old boy with an unusual form of myelomonocytic AML with multiple myeloid sarcomas infiltrating bone and soft tissues. The G-banding analysis together with FISH yielded the karyotype 47,XY, +6,t(8;19;11)(q24;p13;q23). FISH analysis also demonstrated that MLL was split. RNA-sequencing showed that the translocation had generated an MLL-ELL chimera in which exon 9 of MLL (nt 4241 in sequence with accession number NM_005933.3) was fused to exon 6 of ELL (nt 817 in sequence with accession number NM_006532.3). RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript.
Based on our findings and information on a few previously reported patients, we speculate that young age, myelomonoblastic AML, and the presence of extramedullary disease may be typical of children with rare MLL-ELL fusion transcripts.
染色体易位t(11;19)(q23;p13)，其断点位于19p13.1亚带内，主要见于急性髓系白血病（AML），并导致MLL-ELL融合基因。MLL-ELL结构的变异似乎会影响该融合基因在体内的致白血病能力，可能是临床特征差异的原因。目前报道的病例数量非常有限，如果要确定罕见融合的潜在临床意义，增加有关MLL-ELL变异的更多信息至关重要。
对一名20个月大患有一种特殊形式的伴有多个髓系肉瘤浸润骨骼和软组织的髓单核细胞AML男孩的骨髓细胞进行了细胞遗传学和分子遗传学分析。G显带分析结合荧光原位杂交（FISH）得出核型为47,XY,+6,t(8;19;11)(q24;p13;q23)。FISH分析还显示MLL发生了断裂。RNA测序表明该易位产生了一个MLL-ELL嵌合体，其中MLL的外显子9（登录号NM_005933.3序列中的第4241位核苷酸）与ELL的外显子6（登录号NM_006532.3序列中的第817位核苷酸）融合。逆转录聚合酶链反应（RT-PCR）结合桑格测序验证了上述融合转录本的存在。
基于我们的发现以及少数先前报道患者的信息，我们推测年龄小、髓单核细胞AML以及髓外疾病的存在可能是具有罕见MLL-ELL融合转录本儿童的典型特征。
