Limits...
Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.

Suzuki M, Yamagata K, Shino M, Aikawa Y, Akashi K, Watanabe T, Kitabayashi I - Cancer Sci. (2014)

Bottom Line: The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies.Wild-type clathrin assembly lymphoid myeloid leukemia protein (CALM) primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia.These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.

Show MeSH

Related in: MedlinePlus

The nuclear export signal within clathrin assembly lymphoid myeloid leukemia protein (CALM) is sufficient for leukemic transformation by CALM-AF10. (a) Survival of mice injected with murine bone-marrow cells transduced with FLAG-CALM-AF10 or FLAG-NES2-AF10. The leukemia-free survivals of the mice were analyzed. CALM-AF10 primary transplantation, n = 8; CALM-AF10 secondary transplantation, n = 4; NES2-AF10 primary transplantation, n = 4; NES2-AF10 secondary transplantation, n = 9. (b) Peripheral blood smears and bone-marrow cytospins were stained with May-Giemsa from CALM-AF10-transduced or NES2-AF10-transduced bone-marrow cells. Original magnification is 400×. (c) Population of blasts and segmented neutrophils in bone-marrow cells shown in (b). The scale bars represent 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4317939&req=5

fig03: The nuclear export signal within clathrin assembly lymphoid myeloid leukemia protein (CALM) is sufficient for leukemic transformation by CALM-AF10. (a) Survival of mice injected with murine bone-marrow cells transduced with FLAG-CALM-AF10 or FLAG-NES2-AF10. The leukemia-free survivals of the mice were analyzed. CALM-AF10 primary transplantation, n = 8; CALM-AF10 secondary transplantation, n = 4; NES2-AF10 primary transplantation, n = 4; NES2-AF10 secondary transplantation, n = 9. (b) Peripheral blood smears and bone-marrow cytospins were stained with May-Giemsa from CALM-AF10-transduced or NES2-AF10-transduced bone-marrow cells. Original magnification is 400×. (c) Population of blasts and segmented neutrophils in bone-marrow cells shown in (b). The scale bars represent 20 μm.

Mentions: To determine whether CALM-AF10 and NES2-AF10 can induce leukemia in mice, we injected bone-marrow progenitor cells transduced with CALM-AF10 and NES2-AF10 into lethally irradiated mice. Seven out of eight mice transplanted with cells expressing CALM-AF10 developed leukemia within 6 months after transplantation (Fig.3a), and all mice transplanted with cells expressing NES2-AF10 developed leukemia within 3 months after transplantation. When cells prepared from bone marrow of these leukemic mice were transplanted into secondary recipient mice, all recipients promptly developed leukemia (medians: CALM-AF10 donors, 21 days [n = 4]; NES2-AF10 donors, 25 days [n = 9]). Morphological analysis revealed large populations of blast cells in leukemic mice receiving cells transduced with either CALM-AF10 or NES2-AF10 (Fig.3b,c). Flow cytometry analysis showed that cells expressing CALM-AF10 and NES2-AF10 in the bone marrow cells of primary recipient mice were Mac1+, CSF1R+ and c-kit+ (Fig.4a). Moreover, as shown in Figure4b, Hoxa5, Hoxa7, Hoxa9, Hoxa10 and Meis1 expression levels were upregulated in cells expressing CALM-AF10 and NES2-AF10 compared with normal bone marrow cells, although upregulation of Hoxa5 and Meis1 in primary recipient mice harboring NES2-AF10 was not significant (P = 0.084 and P = 0.093, respectively). These data demonstrate that the NES within CALM-AF10 is a critical element for induction of leukemia.


Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.

Suzuki M, Yamagata K, Shino M, Aikawa Y, Akashi K, Watanabe T, Kitabayashi I - Cancer Sci. (2014)

The nuclear export signal within clathrin assembly lymphoid myeloid leukemia protein (CALM) is sufficient for leukemic transformation by CALM-AF10. (a) Survival of mice injected with murine bone-marrow cells transduced with FLAG-CALM-AF10 or FLAG-NES2-AF10. The leukemia-free survivals of the mice were analyzed. CALM-AF10 primary transplantation, n = 8; CALM-AF10 secondary transplantation, n = 4; NES2-AF10 primary transplantation, n = 4; NES2-AF10 secondary transplantation, n = 9. (b) Peripheral blood smears and bone-marrow cytospins were stained with May-Giemsa from CALM-AF10-transduced or NES2-AF10-transduced bone-marrow cells. Original magnification is 400×. (c) Population of blasts and segmented neutrophils in bone-marrow cells shown in (b). The scale bars represent 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317939&req=5

fig03: The nuclear export signal within clathrin assembly lymphoid myeloid leukemia protein (CALM) is sufficient for leukemic transformation by CALM-AF10. (a) Survival of mice injected with murine bone-marrow cells transduced with FLAG-CALM-AF10 or FLAG-NES2-AF10. The leukemia-free survivals of the mice were analyzed. CALM-AF10 primary transplantation, n = 8; CALM-AF10 secondary transplantation, n = 4; NES2-AF10 primary transplantation, n = 4; NES2-AF10 secondary transplantation, n = 9. (b) Peripheral blood smears and bone-marrow cytospins were stained with May-Giemsa from CALM-AF10-transduced or NES2-AF10-transduced bone-marrow cells. Original magnification is 400×. (c) Population of blasts and segmented neutrophils in bone-marrow cells shown in (b). The scale bars represent 20 μm.
Mentions: To determine whether CALM-AF10 and NES2-AF10 can induce leukemia in mice, we injected bone-marrow progenitor cells transduced with CALM-AF10 and NES2-AF10 into lethally irradiated mice. Seven out of eight mice transplanted with cells expressing CALM-AF10 developed leukemia within 6 months after transplantation (Fig.3a), and all mice transplanted with cells expressing NES2-AF10 developed leukemia within 3 months after transplantation. When cells prepared from bone marrow of these leukemic mice were transplanted into secondary recipient mice, all recipients promptly developed leukemia (medians: CALM-AF10 donors, 21 days [n = 4]; NES2-AF10 donors, 25 days [n = 9]). Morphological analysis revealed large populations of blast cells in leukemic mice receiving cells transduced with either CALM-AF10 or NES2-AF10 (Fig.3b,c). Flow cytometry analysis showed that cells expressing CALM-AF10 and NES2-AF10 in the bone marrow cells of primary recipient mice were Mac1+, CSF1R+ and c-kit+ (Fig.4a). Moreover, as shown in Figure4b, Hoxa5, Hoxa7, Hoxa9, Hoxa10 and Meis1 expression levels were upregulated in cells expressing CALM-AF10 and NES2-AF10 compared with normal bone marrow cells, although upregulation of Hoxa5 and Meis1 in primary recipient mice harboring NES2-AF10 was not significant (P = 0.084 and P = 0.093, respectively). These data demonstrate that the NES within CALM-AF10 is a critical element for induction of leukemia.

Bottom Line: The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies.Wild-type clathrin assembly lymphoid myeloid leukemia protein (CALM) primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia.These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus