Hyperfunction of neutrophils in a patient with BCR/ABL negative chronic myeloid leukemia: a case report with in vitro studies.
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.
Department of Hematology-Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
K
K
Watari
A
A
Tojo
T
T
Nagamura-Inoue
M
M
Matsuoka
S
S
Irie
K
K
Tani
Y
Y
Yamada
S
S
Asano
D001853:Bone Marrow / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D020732:Cytogenetic Analysis; D017809:Fatal Outcome; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006111:Graves Disease / Q000150:complications; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016209:Interleukin-8 / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D011110:Polymorphism, Genetic; D011649:Pulmonary Alveolar Proteinosis / Q000150:complications; D013481:Superoxides / Q000378:metabolism; D016463:Sweet Syndrome / Q000150:complications
D016209:Interleukin-8; D013481:Superoxides; D007041:Hypoxanthine Phosphoribosyltransferase; D016044:Fusion Proteins, bcr-abl