AUTHOR=Fournier Benjamin , Balducci Estelle , Duployez Nicolas , Clappier Emmanuelle , Cuccuini Wendy , Arfeuille Chloé , Caye-Eude Aurélie , Delabesse Eric , Bottollier-Lemallaz Colomb Elodie , Nebral Karin , Chrétien Marie-Lorraine , Derrieux Coralie , Cabannes-Hamy Aurélie , Dumezy Florent , Etancelin Pascaline , Fenneteau Odile , Frayfer Jamile , Gourmel Antoine , Loosveld Marie , Michel Gérard , Nadal Nathalie , Penther Dominique , Tigaud Isabelle , Fournier Elise , Reismüller Bettina , Attarbaschi Andishe , Lafage-Pochitaloff Marina , Baruchel André 

TITLE=B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01374

DOI=10.3389/fonc.2019.01374

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> B-cell acute lymphoblastic leukemia associated with t(5;14)(q31;q32); <italic>IGH-IL3</italic> is an exceptional cause of eosinophilia. The <italic>IGH</italic> enhancer on 14q32 is juxtaposed to the <italic>IL3</italic> gene on 5q31, leading to interleukin-3 overproduction and release of mature eosinophils in the blood. Clinical, biological and outcome data are extremely scarce in the literature. Except for eosinophilia, no relevant common feature has been highlighted in these patients. However, it has been classified as a distinct entity in the World Health Organization classification.</p><p><bold>Cases Presentation:</bold> Eight patients with t(5;14)(q31;q32) treated by French or Austrian protocols were retrospectively enrolled. Array comparative genomic hybridization, multiplex ligation-dependent probe amplification or genomic PCR search for <italic>IKZF1</italic> deletion were performed in 7. Sixteen patients found through an exhaustive search in the literature were also analyzed.</p><p>For those 24 patients, median age at diagnosis is 14.3 years with a male predominance (male to female ratio = 5). Eosinophilia-related symptoms are common (neurologic in 26%, thromboembolic in 26% or pulmonary in 50%). Median white blood cells count is high (72 × 10<sup>9</sup>/L) and linked to eosinophilia (median: 32 × 10<sup>9</sup>/L). Peripheral blasts are present at a low level or absent (median: 0 × 10<sup>9</sup>/L; range: 0–37 × 10<sup>9</sup>/L). Bone marrow morphology is marked by a low blast infiltration (median: 42%). We found an <italic>IKZF1</italic> deletion in 5 out of 7 analyzable patients Outcome data are available for 14 patients (median follow-up: 28 months): 8 died and 6 are alive in complete remission.</p><p>Some of these features are concordant with those seen in patients with other <italic>IGH</italic>-rearranged B-cell acute lymphoblastic leukemias: young age at onset, male sex, low blast count, high incidence of <italic>IKZF1</italic> deletion and intermediate prognosis.</p><p><bold>Conclusion:</bold> Based on shared epidemiological and biological features, B-cell acute lymphoblastic leukemia with t(5;14)(q31;q32) is a peculiar subset of <italic>IGH</italic>-rearranged B-cell acute lymphoblastic leukemia with an intermediate prognosis and particular clinical features related to eosinophilia.</p>