IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells

  • Authors:
    • Kei Suzuki
    • Ryoichi Ono
    • Kohshi Ohishi
    • Masahiro Masuya
    • Itaru Kataoka
    • Bing Liu
    • Yoshiki Nakamori
    • Kazuko Ino
    • Fumihiko Monma
    • Hirofumi Hamada
    • Toshio Kitamura
    • Naoyuki Katayama
    • Tetsuya Nosaka
  • View Affiliations

  • Published online on: September 7, 2011     https://doi.org/10.3892/ijo.2011.1192
  • Pages: 53-62
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Abstract

The BCR-ABL1 induces chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). Recent studies revealed high ratios of loss of the IKZF1 gene which encodes IKAROS in BCR-ABL1+ ALL and lymphoblastic crisis (LBC) of CML. However, little is known about the cooperativity between the aberrant IKAROS and BCR-ABL1 in primary human hematopoietic cells. We investigated the effects of expression of BCR-ABL1 and/or IK6, a natural dominant negative isoform of IKAROS, on proliferation and differentiation of human CD34+ cord blood cells with or without human bone marrow-derived stromal cells which support early B cell differentiation. Cell proliferation was remarkably enhanced by co-expression of BCR-ABL1 and IK6, with reduced expression of glycophorin A and increased expression of CD41, especially on stromal cells, compared with expression of BCR-ABL1 alone that resulted in expansion of erythroid progenitors. Interestingly, p190BCR-ABL1 showed higher dependency on stromal cells to stimulate cell growth with IK6, than p210BCR-ABL1. Furthermore, the cooperation was found to depend on direct cell adhesive interaction of hematopoietic progenitors with stromal cells. These findings suggest that IK6 and BCR-ABL1 synergistically contribute to leukemogenesis in human bone marrow stromal microenvironment, and may provide a clue to elucidate the mechanisms of leukemogenesis of Ph+ ALL and CML-LBC.

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January 2012
Volume 40 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Suzuki, K., Ono, R., Ohishi, K., Masuya, M., Kataoka, I., Liu, B. ... Nosaka, T. (2012). IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells. International Journal of Oncology, 40, 53-62. https://doi.org/10.3892/ijo.2011.1192
MLA
Suzuki, K., Ono, R., Ohishi, K., Masuya, M., Kataoka, I., Liu, B., Nakamori, Y., Ino, K., Monma, F., Hamada, H., Kitamura, T., Katayama, N., Nosaka, T."IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells". International Journal of Oncology 40.1 (2012): 53-62.
Chicago
Suzuki, K., Ono, R., Ohishi, K., Masuya, M., Kataoka, I., Liu, B., Nakamori, Y., Ino, K., Monma, F., Hamada, H., Kitamura, T., Katayama, N., Nosaka, T."IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells". International Journal of Oncology 40, no. 1 (2012): 53-62. https://doi.org/10.3892/ijo.2011.1192