The present disclosure relates generally to methods of treating hematopoietic cell malignancy in a subject by administering to the subject a Hedgehog (Hh) pathway antagonist, such as a Smoothen (Smo) antagonist alone or in combination with an ABL-kinase antagonist. Specifically, the disclosure relates to a method of treating hematopoietic cell malignancy in a subject by administering the Hh pathway antagonist, such as the Smo antagonist cyclopamine, in combination with the ABL-kinase antagonist imatinib.