It is intended to provide a tool, a procedure and so on which are useful in developing a therapeutic strategy efficacious in inhibiting or overcoming the resistance against a CD20-directed molecular-targeted drug. Thus, a CD20-negatively converted B-cell malignant lymphocyte cell line is provided. Also, a model animal indicating the pathological conditions of CD20-negatively converted B-cell malignant lymphocyte is provided. Further, a method of screening a substance, which is efficacious against CD20-positive B-cell malignant lymphocyte or CD20-negatively converted B cell malignant lymphocyte, is provided. Furthermore, a drug against CD20-positive B-cell malignant lymphocyte or CD20-negatively converted B-cell malignant lymphocyte, which is characterized by being used together with a CD20-directed molecular-targeted drug, is provided. In one embodiment, a DNA methylase inhibitor or a histone deacetylase inhibitor is employed as the active ingredient.