B-ALL With t(5;14)(q31;q32); IGH-IL3 rearrangement and eosinophilia: A comprehensive analysis of peculiar IGH-rearranged B-ALL

Benjamin Fournier (1) , Estelle Balducci (2) , Nicolas Duployez (3) , Emmanuelle Clappier (4) , Wendy Cuccuini (4) , Chloe Arfeuille (1) , Aurelie Caye-Eude (1) , Eric Delabesse (5) , Elodie Bottollier-Lemallaz Colomb (6) , Karin Nebral (7) , Marie-Lorraine Chretien (8) , Coralie Derrieux (9) , Aurelie Cabannes-Hamy (6) , Florent Dumezy (10) , Pascaline Etancelin (11) , Odile Fenneteau (12) , Jamile Frayfer (13) , Antoine Gourmel (14) , Marie Loosveld (15) , Gerard Michel (16) , Nathalie Nadal (6) , Dominique Penther (11) , Isabelle Tigaud (17) , Elise Fournier (18) , Bettina Reismueller (19) , Andishe Attarbaschi (19) , Marina Lafage-Pochitaloff (20) , Andre Baruchel (21, 4)

1 Centre Hospitalier Universitaire Robert Debré
2 Hôpital Paul Brousse
3 Centre de Biologie et de Pathologie - Laboratoire d'Hématologie [CHRU Lille]
4 AP-HP - Hopital Saint-Louis [AP-HP]
5 CRCT - Centre de Recherches en Cancérologie de Toulouse
6 CHU Dijon
7 St. Anna Children’s Cancer Research Institute CCRI [Vienna]
8 Service d'Hématologie Clinique (CHU de Dijon)
9 Service d'immuno-hématologie pédiatrique [CHU Necker]
10 Service d'Hématologie Cellulaire [Lille]
11 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
12 Service d'Hématologie Biologique [Hôpital Robert Debré, Paris]
13 Centre Hospitalier de Meaux
14 CHU Amiens-Picardie
15 CIML - Centre d'Immunologie de Marseille - Luminy
16 FEMTO-ST - Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174)
17 Laboratory of Hematology, Centre Hospitalier Lyon Sud
18 SMS - Service des Maladies du Sang [CHU Lille]
19 St. Anna Children's Hospital - Saint Anna Children's Hospital [Vienne] = St Anna Kinderspital
20 APHM - Assistance Publique - Hôpitaux de Marseille
21 Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris]

Background: B-cell acute lymphoblastic leukemia associated with t(5;14)(q31;q32); IGH-IL3 is an exceptional cause of eosinophilia. The IGH enhancer on 14q32 is juxtaposed to the IL3 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. Cases Presentation: 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 IKZF1 deletion were performed in 7. Sixteen patients found through an exhaustive search in the literature were also analyzed. 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 x 10(9)/L) and linked to eosinophilia (median: 32 x 10(9)/L). Peripheral blasts are present at a low level or absent (median: 0 x 10(9)/L; range: 0-37 x 10(9)/L). Bone marrow morphology is marked by a low blast infiltration (median: 42%). We found an IKZF1 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. Some of these features are concordant with those seen in patients with other IGH-rearranged B-cell acute lymphoblastic leukemias: young age at onset, male sex, low blast count, high incidence of IKZF1 deletion and intermediate prognosis. Conclusion: Based on shared epidemiological and biological features, B-cell acute lymphoblastic leukemia with t(5;14)(q31;q32) is a peculiar subset of IGH-rearranged B-cell acute lymphoblastic leukemia with an intermediate prognosis and particular clinical features related to eosinophilia.

Domaines: Immunologie

Benjamin Fournier, Estelle Balducci, Nicolas Duployez, Emmanuelle Clappier, Wendy Cuccuini, et al.. B-ALL With t(5;14)(q31;q32); IGH-IL3 rearrangement and eosinophilia: A comprehensive analysis of peculiar IGH-rearranged B-ALL. Frontiers in Oncology, 2019, 9, pp.01374. ⟨10.3389/fonc.2019.01374⟩. ⟨hal-02475039⟩