Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH)

Norimitsu Inoue, Tomohisa Izui-Sarumaru, Yoshiko Murakami, Yuichi Endo, Jun Ichi Nishimura, Ken Kurokawa, Maki Kuwayama, Hiroaki Shime, Takashi Machii, Yuzuru Kanakura, Gabrielle Meyers, Carl Wittwer, Zhong Chen, William Babcock, Debra Frei-Lahr, Charles J. Parker, Taroh Kinoshita

Research output: Contribution to journalArticle

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Abstract

Somatic mutation of PIGA in hematopoietic stem cells causes deficiency of glycosyl phosphatidylinositol-anchored proteins in paroxysmal nocturnal hemoglobinuria (PNH) that underlies the intravascular hemolysis but does not account for expansion of the PNH clone. Immune mechanisms may mediate clonal selection but appear insufficient to account for the clonal dominance necessary for PNH to become clinically apparent. Herein, we report 2 patients with PNH whose PIGA-mutant cells had a concurrent, acquired rearrangement of chromosome 12. In both cases, der(12) had a break within the 3′ untranslated region of HMGA2, the architectural transcription factor gene deregulated in many benign mesenchymal tumors, that caused ectopic expression of HMGA2 in the bone marrow. These observations suggest that aberrant HMGA2 expression, in concert with mutant PIGA, accounts for clonal hematopoiesis in these 2 patients and suggest the concept of PNH as a benign tumor of the bone marrow.

Original languageEnglish (US)
Pages (from-to)4232-4236
Number of pages5
JournalBlood
Volume108
Issue number13
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

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Paroxysmal Hemoglobinuria
Hematopoiesis
Tumors
Bone
Glycosylphosphatidylinositols
3' Untranslated Regions
Chromosomes
Stem cells
Transcription Factors
Genes
Bone Marrow
Chromosomes, Human, Pair 12
Hematopoietic Stem Cells
Hemolysis
Proteins
Neoplasms
Clone Cells
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Inoue, N., Izui-Sarumaru, T., Murakami, Y., Endo, Y., Nishimura, J. I., Kurokawa, K., ... Kinoshita, T. (2006). Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood, 108(13), 4232-4236. https://doi.org/10.1182/blood-2006-05-025148

Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). / Inoue, Norimitsu; Izui-Sarumaru, Tomohisa; Murakami, Yoshiko; Endo, Yuichi; Nishimura, Jun Ichi; Kurokawa, Ken; Kuwayama, Maki; Shime, Hiroaki; Machii, Takashi; Kanakura, Yuzuru; Meyers, Gabrielle; Wittwer, Carl; Chen, Zhong; Babcock, William; Frei-Lahr, Debra; Parker, Charles J.; Kinoshita, Taroh.

In: Blood, Vol. 108, No. 13, 15.12.2006, p. 4232-4236.

Research output: Contribution to journalArticle

Inoue, N, Izui-Sarumaru, T, Murakami, Y, Endo, Y, Nishimura, JI, Kurokawa, K, Kuwayama, M, Shime, H, Machii, T, Kanakura, Y, Meyers, G, Wittwer, C, Chen, Z, Babcock, W, Frei-Lahr, D, Parker, CJ & Kinoshita, T 2006, 'Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH)', Blood, vol. 108, no. 13, pp. 4232-4236. https://doi.org/10.1182/blood-2006-05-025148
Inoue N, Izui-Sarumaru T, Murakami Y, Endo Y, Nishimura JI, Kurokawa K et al. Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood. 2006 Dec 15;108(13):4232-4236. https://doi.org/10.1182/blood-2006-05-025148
Inoue, Norimitsu ; Izui-Sarumaru, Tomohisa ; Murakami, Yoshiko ; Endo, Yuichi ; Nishimura, Jun Ichi ; Kurokawa, Ken ; Kuwayama, Maki ; Shime, Hiroaki ; Machii, Takashi ; Kanakura, Yuzuru ; Meyers, Gabrielle ; Wittwer, Carl ; Chen, Zhong ; Babcock, William ; Frei-Lahr, Debra ; Parker, Charles J. ; Kinoshita, Taroh. / Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). In: Blood. 2006 ; Vol. 108, No. 13. pp. 4232-4236.
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