Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2018 Apr 24

PMID 29681510

Citations 97

Authors

Michelle L Churchman

Maoxiang Qian

Geertruy Te Kronnie

Ranran Zhang

Wenjian Yang

Hui Zhang

Tobia Lana

Paige Tedrick

Rebekah Baskin

Katherine Verbist

Jennifer L Peters

Meenakshi Devidas

Eric Larsen

Ian M Moore

Zhaohui Gu

Chunxu Qu

Hiroki Yoshihara

Shaina N Porter

Shondra M Pruett-Miller

Gang Wu

Elizabeth Raetz

Paul L Martin

W Paul Bowman

Naomi Winick

Elaine Mardis

Robert Fulton

Martin Stanulla

William E Evans

Mary V Relling

Ching-Hon Pui

Stephen P Hunger

Mignon L Loh

Rupert Handgretinger

Kim E Nichols

Jun J Yang

Charles G Mullighan

Affiliations

Soon will be listed here.

Abstract

Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.

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