Figure 4.
Figure 4. Expression of mutant NFE2 causes AML with concomitant granulocytic sarcoma as well as isolated granulocytic sarcoma in mice. (A) Diagnoses according to the Bethesda Classification of Nonlymphoid Hematological Malignancies10 in n = 41 mice expressing various NFE2 mutations9 (B-E) Protein nomenclature of indicated NFE2 mutants, s. supplemental Table 2. (B) Hematological parameters of selected mice that developed leukemia. WBC: white blood cells; HCT, hematocrit; PLT, platelets. Blood counts indicating leukocytosis, anemia, and thrombocytopenia, the clinical hallmarks of leukemia, are highlighted in the black boxes. (C) FACS analysis of PB leukocytes of mouse #539 and #40. Cells were stained with CD11b and Ly6G/C or CD3ε and CD45R to determine myeloid and lymphoid cells, respectively. (D) From left to right: PB smear of mouse #539 (1000×) and chloracetate esterase (CAE) stained femur section of mouse #40 (400× and 1000×). (E) Histological analysis, hematoxylin and eosin–stained sections of the following organs of leukemic mice: #539 (from left to right): femur (1000×), liver (1000×), kidney (10× and 1000×). #535 (from left to right): femur (1000×), kidney (10× and 1000×). #537 (from left to right): femur (400× and 1000×), lung (400×). #40 (from left to right): sarcoma (400×), lung (400× and 1000×). #32 (from left to right): top: femur (400× and 1000×), liver (400× and 1000×); bottom: lung (25× and 1000×). Bars: 200 μm (10×), 500 μm (25×), 50 μm (400×), 20 μm (1000×).

Expression of mutant NFE2 causes AML with concomitant granulocytic sarcoma as well as isolated granulocytic sarcoma in mice. (A) Diagnoses according to the Bethesda Classification of Nonlymphoid Hematological Malignancies10  in n = 41 mice expressing various NFE2 mutations (B-E) Protein nomenclature of indicated NFE2 mutants, s. supplemental Table 2. (B) Hematological parameters of selected mice that developed leukemia. WBC: white blood cells; HCT, hematocrit; PLT, platelets. Blood counts indicating leukocytosis, anemia, and thrombocytopenia, the clinical hallmarks of leukemia, are highlighted in the black boxes. (C) FACS analysis of PB leukocytes of mouse #539 and #40. Cells were stained with CD11b and Ly6G/C or CD3ε and CD45R to determine myeloid and lymphoid cells, respectively. (D) From left to right: PB smear of mouse #539 (1000×) and chloracetate esterase (CAE) stained femur section of mouse #40 (400× and 1000×). (E) Histological analysis, hematoxylin and eosin–stained sections of the following organs of leukemic mice: #539 (from left to right): femur (1000×), liver (1000×), kidney (10× and 1000×). #535 (from left to right): femur (1000×), kidney (10× and 1000×). #537 (from left to right): femur (400× and 1000×), lung (400×). #40 (from left to right): sarcoma (400×), lung (400× and 1000×). #32 (from left to right): top: femur (400× and 1000×), liver (400× and 1000×); bottom: lung (25× and 1000×). Bars: 200 μm (10×), 500 μm (25×), 50 μm (400×), 20 μm (1000×).

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