Compositions and methods for the identification, prognosis, classification, treatment, and diagnosis of leukemia or a genetic predisposition to leukemia are provided. The present invention is based on the discovery of various genomic abnormalities of the IKZF1 gene which are shown herein to be associated with acute lymphoblastic leukemia (ALL), more particularly, associated with BCR-ABL1 positive ALL and/or shown to be associated with chronic myeloid leukemia (CML), more particularly, associated with blast crisis chronic myeloid leukemia (BC-CML) and/or the likelihood of progression into blastic transformation of CML. These various genomic abnormalities of the IKZF1 gene can further be used as prognostic markers to identify a subgroup of ALL having very poor outcomes. Such genomic abnormalities of IKZF1 find use in methods and compositions useful in the identification and/or prognosis and/or predisposition and/or treatment of ALL, more particularly, BCR-ABL1 positive ALL and/or in the identification and/or prognosis and/or predisposition and/or treatment of CML, more particularly, of BC-CML and/or the likelihood of progression into blastic transformation of CML and/or as prognostic markers to identify a subgroup of ALL having very poor outcomes.

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