Trisomy of Chromosome 7: a Novel Cytogenetic Abnormality in a Paediatric Case of Mixed Acute Leukemia.
Authors: Parasole Rosanna , Vicari Laura , Petruzziello Fara , Leszl Anna , Menna Giuseppe , Tarsitano M. , Del Vecchio Luigi , Scalia Giulia , Maisto Giovanna , Basso Giuseppe , Poggi Vincenzo , Marra Nicoletta 
Published: October 2019

Abstract
Abstract 4121

Background
Mixed acute leukemias are an heterogeneous category of poorly differentiated leukemias, affecting people of all ages. These forms of leukemias are very rare, 3-5% of all acute leukemias, and are characterized by co-expression of myeloid and lymphoid associated-antigens on the same leukemic cells. The therapeutic approach is not defined because, often, mixed leukemias switch their lineage of origin during treatment and the prognosis is very poor.
We describe a novel, never reported before, cytogenetic abnormality in a child with a mixed acute leukemia.

Methods
On January 2009, a nonsyndromic 5 year-old boy was admitted at our Institution for an acute hyperleukocytosic leukemia (WBC > 100.000/L). The patient showed spleen enlargement and massive mediastinal lymphadenopathy. Morphological diagnosis of acute leukemia was based on the French-American-British criteria and the immunophenotypic diagnosis was performed by flow cytometry using a large panel of leukemia-associated antibodies (myeloid and B/T lymphoid markers). Cytogenetic analysis was performed on unstimulated overnight culture of bone marrow, followed by RHG-banding. The expression of T-cell receptor and rearrangement of heavy chain immunoglobulin was assessed by molecular methodology.

Results
Morphologic evaluation showed lymphoid blasts according to the FAB-L2 classification with same aberrations such as myeloid blebs and prominent nucleoli. The immunophenotype showed mixed expression of myeloid markers (MPO > 3%, CD33, CD11a, CD11b, CD117) and T lymphoid antigens (surface CD7, CD99 and cytoplasmic CD3) and an aberrant lineage-B expression (CD19). On the basis of these data the diagnosis of acute mixed leukemia was carried out. Cytogenetic analysis showed trisomy of chromosome 7, a chromosomal aberration never reported before in acute myeloid or lymphoid leukemia (figure 1). Ig or T-cell receptor gene rearrangements were not identified as well as translocations commonly found in either lymphoid and myeloid leukemias. The treatment was initially performed according to the acute lymphoblastic leukemia protocol (AIEOP ALL2000) but unresponsiveness as seen up to day +12 required a shift to a mixed personalized protocol with cyclophosphamide, dexamethasone and L-asparaginase associated with more specific drugs for myeloid lineage such as high dose cytarabine and etoposide. After a febrile aplasia, bone marrow reconstitution showed about 75% of mixed blasts. So the child shifted to a rescue protocol with fludarabine, cytarabine, idarubicine (FLA-Ida) repeated 2 times with a good haematological and cytometric response (0,9% of blasts). For consolidation of remission, was performed 1 cycle with clofarabine, cyclophosphamide and etoposide followed by 1 cycle with clofarabine and cytarabine with a minor response (1,9% of blasts by immunophenotype). Actually, the child is undergoing an unrelated mismatched transplant.

Conclusion
At the best of our knowledge, this case is the first report of trisomy 7 in a mixed acute leukemia in childhood. The only cytogenetic aberration known so far in pediatric mixed leukemias are: isochromosome 7, monosomy 7, or inversion 7 as well as translocations such as t(1;7), t(4;7) or t(7;15). Trisomy 7 is also described in some mesenchymal and neurogenic neoplasms such as brain, colon, ovary, prostate, bladder and kidney tumors and also in some non-neoplastic inflammatory disease such as rheumatoid arthritis and osteoarthritis. In haematological field, trisomy 7 is reported only in few cases of myeloma, non-Hodgkin lymphoma and amyloidosis. The prognostic significance of this cytogenetic aberration in mixed acute leukemias is still unknown.

Disclosures:
No relevant conflicts of interest to declare.