Background: Among patients diagnosed with chronic myeloid leukemia (CML), a small percentage lack a BCR/ABL fusion gene, a landmark of CML. Their clinical features are distinct from patients with BCR/ABL positive CML, although to the authors' knowledge the pathogenesis to date has been unknown.
Methods: A 50-year-old female patient with BCR/ABL negative CML and multiple complications of Graves disease, Sweet syndrome, and a fatal pulmonary alveolar proteinosis (PAP) is described in the current study. To show a clonal origin of her myeloid cells, hypoxanthine phosphoribosyltransferase (HPRT) assay was applied. Because the patient developed a progressive and fatal neutrophilia, a screening of cell functions in neutrophilic lineage, including in vitro colony assay of her bone marrow cells and production of superoxide and interleukin-8 (IL-8) by blood neutrophils was performed.
Results: Southern blot analysis based on the polymorphism of the HPRT gene was compatible with monoclonality of her neutrophils. The patient had an increased amount of bone marrow granulocyte-macrophage progenitor cells, which formed colonies in response to a very low dose (0.1 ng/mL) of granulocyte-colony stimulating factor. In vitro production of superoxide and IL-8, which is an inducer of positive chemotaxis of neutrophils, by her peripheral neutrophils was markedly augmented. Her bronchoalveolar lavage fluid also contained a significant amount of IL-8 as well as an unusual infiltration of neutrophils.
Conclusions: In the patient in the current study, hyperfunction of the neutrophils might have contributed to the onset of PAP as well as Sweet syndrome and to the pathogenesis of BCR/ABL negative CML.
Copyright 2000 American Cancer Society.