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Chronic neutrophilic leukemia (CNL) is a very rare myeloproliferative disorder. To determine the neoplastic origin of CNL, morphological and cytogenetical studies were made of colonies derived from hematopoietic progenitors of a patient with CNL. The patient's hematopoietic progenitors spontaneously formed colonies consisting of mature granulocytes, and cytogenetical study of the colonies indicated chromosome abnormalities identical to those in the patient's bone marrow cells. Analysis of colonies consisting of granulocytes and macrophages, macrophages, or erythrocytes disclosed a normal karyotype. These results demonstrated that the neoplastic process in this patient with CNL originated in hematopoietic progenitors capable of differentiating only into granulocytes, and not granulocytes and monocytes, monocytes, or erythrocytes.

Chronic neutrophilic leukemia (CNL) is a very rare myeloproliferative disorder. To determine the neoplastic origin of CNL, morphological and cytogenetical studies were made of colonies derived from hematopoietic progenitors of a patient with CNL. The patient's hematopoietic progenitors spontaneously formed colonies consisting of mature granulocytes, and cytogenetical study of the colonies indicated chromosome abnormalities identical to those in the patient's bone marrow cells. Analysis of colonies consisting of granulocytes and macrophages, macrophages, or erythrocytes disclosed a normal karyotype. These results demonstrated that the neoplastic process in this patient with CNL originated in hematopoietic progenitors capable of differentiating only into granulocytes, and not granulocytes and monocytes, monocytes, or erythrocytes. Am. J. Hematol. 57:221-224, 1998.

We previously established a cell line from a patient with acute myelomonocytic leukemia with eosinophilia (M4E0), ME-1. ME-1 cells are responsive to colony-stimulating factors (CSFs) such as interleukin-3 (IL-3), IL-4, and granulocyte-macrophage CSF (GM-CSF), and exhibit monocyte-macrophage differentiation. We isolated three subclones, ME-F1 from ME-1, and ME-F2 and ME-F3 from two sublines of ME-1. These subclones had different morphologic, cytochemical, phenotypic, and cytogenetic features. They represented different monocytic-lineage differentiation stages and exhibited different responses to IL-3, GM- CSF, and especially IL-4. IL-3, GM-CSF, and IL-4 enhanced proliferation and differentiation to macrophage-like cells in the ME-F1 subclone. However, they enhanced only proliferation of ME-F2 cells and only differentiation to macrophage-like cells in the ME-F3 subclone. To elucidate possible differences in signal transduction mechanisms in ME- F1, ME-F2, and ME-F3 cells following stimulation by CSFs, we studied the effects of IL-3 and IL-4 on protein kinase C (PKC) activity. Both IL-3 and IL-4 induced a rapid, transient decrease of cytosolic PKC in ME-F1 cells, but did not affect PKC activity in ME-F2 and ME-F3 cells. The PKC inhibitors, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H- 7) and calphostin C inhibited IL-3-induced enhancement of proliferation and differentiation of ME-F1 cells, but did not inhibit enhancement of proliferation of ME-F2 cells and differentiation of ME-F3 cells. Our data suggest that PKC-dependent signal transduction is considerably related to IL-3-induced proliferation and differentiation of ME-F1 cells. In addition, it was demonstrated that the two subclones, ME-F2 and ME-F3, lost one of the two responses of ME-F1 cells to CSFs, either proliferation or differentiation, and simultaneously lost PKC-dependent response to CSFs.

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