Deletion of the long arm of chromosome 20 in a patient with chronic neutrophilic leukemia: Cytogenetic findings in chronic neutrophilic leukemia

We encountered a 67-year-old female with chronic neutrophilic leukemia (CNL). Cytogenetic study showed she had a deletion in the long arm of chromosome 20. This finding indicates that CNL, in this case, is a clonal disorder. Most CNL patients have normal karyotypes, and only four patients with cytogenetic abnormalities, including two cases who received chemotherapy before the cytogenetic abnormality was detected, have been reported. Four of those cases, including our case, had abnormalities in the long arm of chromosome 20. This locus may be associated with the development of CNL. To our knowledge, this is the first case with CNL who showed deletion of the long arm of chromosome 20 before treatment was started. Am. J. Hematol. 54:72–75, 1997 © 1997 Wiley-Liss, Inc.     

Acute lymphoblastic leukemia in a patient with chronic cyanoacrylate exposure

Environmental agents have long been thought to be linked to the development of malignancies. Due to the difficulty in identifying and verifying exposures to such agents, only a few chemical compounds are clearly linked to malignancies. We report here the case of a 36-year-old man with pre-B cell acute lymphoblastic leukemia. This patient was using industrial strength glue to reattach a chipped tooth for approximately 1 year, and such use was associated with chronic exposure of his oral mucosa to this glue. This case raises the possibility that chronic exposure to cyanoacrylates, the adhesive agents in industrial strength glue, may be associated with the development of acute lymphoblastic leukemia in humans.     

Granulocyte-colony stimulating factor-producing myeloma with clinical manifestations mimicking chronic neutrophilic leukemia

A 68-year-old man was diagnosed as having bronchial asthma in November 1996. He presented with leukocytosis in June 2002. The WBC count was 29,900/microliter with 82% mature neutrophils showing toxic granules. The neutrophil alkaline phosphatase score and serum level of vitamin B12 were elevated. Bone marrow demonstrated myeloid hyperplasia and plasmacytosis. Cytogenetic and molecular analyses were negative for Philadelphia chromosome and BCR/ABL fusion gene. Lambda-type Bence-Jones protein was detected on the serum and urinary immunoelectrophoresis. The coexistence of chronic neutrophilic leukemia and myeloma was suspected based on the clinical features. The serum level of granulocyte-colony stimulating factor (G-CSF) was elevated. Immunohistochemically, atypical plasma cells were positive for anti G-CSF antibody. Finally, we diagnosed this patient as having a G-CSF-producing myeloma. Treatment with melphalan and prednisolone was initiated without beneficial response. He was then admitted to our hospital for ROAD therapy (ranimustine, vincristine, melphalan, and dexamethasone). The neutrophil count decreased in parallel with the serum G-CSF level. These observations indicated that the neutrophilia in this case was probably caused by a reactive response to G-CSF secreted from the myeloma cells.     

Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined

The World Health Organization (WHO) classification of myeloid disorders has provided updated parameters for the consistent diagnosis of two previously less than optimally defined chronic myeloid disorders, CNL and CMML. The classification of these disorders, which had been controversial, is now better defined and provides more clinically and biologically relevant disease definitions to enable uniform diagnosis and a framework to evaluate natural history and therapeutic interventions. CNL is now recognized as a distinct entity among the chronic myeloproliferative disorders and CMML is included within the new category of 'myelodysplastic/myeloproliferative diseases' (MDS/MPD). Predominant neutrophilia defines CNL whereas CMML is defined by predominant and monocytosis. In each case these defining features must be distinguished from reactive causes for the same in the absence of clear evidence of myeloid clonality (CNL and CMML) or dysplasia (CMML). The exclusion of underlying bcr/abl-driven oncogenesis is an essential component in the diagnosis of these chronic leukemic processes. The optimal therapy for both CNL and CMML remains uncertain. Current management decisions are based on small studies or extrapolated from therapeutic strategies that are effective in similar chronic, clonal myeloid disorders. Given the potential for evolution to acute leukemia or progressive refractory leucocytosis or cytopenias, allogeneic stem cell transplantation might be appropriate for younger patients. Continued reporting and investigation of specific therapeutic strategies and responses must be encouraged.     

A case of chronic neutrophilic leukemia with trisomy 8

The authors describe a case of chronic neutrophilic leukemia (CNL) showing trisomy of chromosome 8. This anomaly, particularly common in cases of myelodysplastic syndrome (MDS), has never been previously found to be associated with this rare type of leukemia. Thus CNL may occasionally be cytogenetically indistinguishable from cases of MDS.     

Neutrophil function and cytokine-specific signaling in chronic neutrophilic leukemia

We diagnosed an 86-year-old woman with chronic neutrophilic leukemia (CNL) because she showed sustained leukocytosis dominated by mature neutrophils, hepatosplenomegaly, high neutrophilic alkaline phosphatase score, absence of the Ph chromosome, low serum level of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and no evidence of leukemoid reaction. We found that the extent of stimulation of her neutrophil functions by G-CSF and GM-CSF was greatly reduced compared to healthy donars neutrophils. We showed that CNL neutrophils have intact expression of granulocyte colony-stimulating factor receptor (G-CSFR) and granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR). This suggests that failure of enhancement by G-CSF and GM-CSF in CNL neutrophil functions might be due to disturbances in the intracellular domains of G-CSFR and GM-CSFR, regardless of external cytokine stimulation. However, the patient's neutrophils did not show any mutations in the G-CSFR and GM-CSFR intracellular critical regions. We also showed that stat3 and mitogen-activated protein kinase activation by G-CSF or GM-CSF in the patient's neutrophils were significantly lower than those in healthy donor neutrophils. These results suggest that deficiency of CNL neutrophil function might be due to insufficiency of some inflammatory cytokine-specific signaling. Hence, we are the first to show that CNL neutrophils have partially insufficiency in some cytokine-specific signaling. Further studies are needed to elucidate the signal transduction pathways relating to functional defects in CNL neutrophils.     

Clonal expansion after bone marrow transplantation in a patient with chronic myelogenous leukemia

Summary A patient with chronic myelogenous leukemia (CML) having the standard [t(9; 22), Ph] translocation is presented where the Philadelphia (Ph) chromosome disappeared following bone marrow transplantation (BMT). The Ph chromosome reappeared in host cells after one year of stable hematologic remission. Three additional cell lines, all possessing the Ph chromosome with other abnormalities were consistently present in her marrow cells. Two years after BMT, ninety percent of her dividing bone marrow cells had become leukemic. The patient's clinical status remains unchanged, despite complex cytogenetic findings. The high incidence of multiple aberrant leukemic clones present in this case remains intriguing. Possible mechanisms for this unique transformation after BMT are discussed.     

Chimeric del20q in a case of chronic neutrophilic leukemia

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder in which recurrent abnormalities of chromosome 20 have been reported. We report the case of a 76-year-old woman with CNL with partial deletion of the long arm of chromosome 20 in a subset of bone marrow metaphases, suggesting coexistence of a clonal stem cell disorder and normal hematopoiesis. Review of the literature suggests that such mosaicism is common in CNL, possibly accounting for the favorable prognosis observed in many patients with this disorder.     

Hydroxyurea-induced pneumonitis in a patient with chronic idiopathic myelofibrosis after prolonged drug exposure

We describe a 63-yr-old patient diagnosed with chronic idiopathic myelofibrosis whose disease was treated with hydroxyurea for 2 yr. He developed respiratory symptoms that were extensively investigated including lung biopsy. Clinical, radiological and histological features were compatible with a diagnosis of hydroxyurea-induced pneumonitis. Following drug withdrawal there was remarkable improvement in clinical and radiological findings.     

A case of chronic neutrophilic leukemia with original chromosomal abnormalities

We report a new case of the unusual myeloproliferative syndrome chronic neutrophilic leukemia (CNL) that met all the criteria generally required for the diagnosis of this entity. The patient presented abnormalities in platelet function not previously reported that may explain the bleeding tendency observed in these patients. The study of neutrophil function suggested also defective mobility and intracellular bactericidal activity. The chromosomal study revealed original abnormalities consisting of multiple chromosomal ruptures and figures. The disease was controlled with busulfan. After 20 months, the patient died of sepsis. An autopsy was performed confirming the diagnosis and ruling out the existence of a cause of a leukemoid reaction, such as cancer or granulomatous disease.     

Cytofluorometric detection of chronic myelocytic leukemia supervening in a patient with chronic lymphocytic leukemia

An 82-year-old woman with stage I chronic lymphocytic leukemia presented with systemic symptoms, minimal adenopathy, hepatosplenomegaly, and anemia five years after the initial diagnosis was made and while receiving no therapy. Her white blood cell count was 231,000/mm3 with an absolute neutrophil count of 164,360/mm3 and lymphocyte count of 43,890/mm3. Peripheral blood smear inspection revealed both increased mature lymphocytes and myeloid cells at all stages of maturation. Flow cytometric analysis of forward- and right-angle light scatters demonstrated the presence of two populations of cells, one lymphoid, bearing predominantly lambda light chain surface immunoglobulin and showing phenotypic characteristics of B cell chronic lymphocytic leukemia (HLA-DR-positive, BL-1-positive, BL-2-positive, BL-7-positive, Leu-1-positive, Leu-10-positive, BL-5-negative, BL-6-negative, and OKM1-negative), and another granulocytic population expressing phenotypic features compatible with myeloid lineage (HLA-DR-negative, Leu-1-negative, BL-1-negative, BL-2-negative, BL-7-negative, Leu-10-negative, BL-5-positive, BL-6-negative, OKM1-positive, and surface immunoglobulin-negative). All of the peripheral blood cell metaphases were Philadelphia chromosome-positive after 24 hours of culture, confirming the diagnosis of chronic myelocytic leukemia, whereas all of the Epstein-Barr virus-treated B lymphocyte metaphases showed a normal karyotype after two weeks of culture. In this patient, analysis of surface antigens and immunoglobulin fractions by flow cytometry proved to be useful in recognizing concomitantly expressed leukemic lineages. This approach allows the increasing recognition of the heterogeneity of leukemic populations.