Kohsuke Yanagisawa

Neoplastic involvement of granulocytic lineage, not granulocytic-monocytic, monocytic, or erythrocytic lineage, in a patient with chronic neutrophilic leukemia case report

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 patients hematopoietic progenitors spontaneously formed colonies consisting of mature granulocytes, and cytogenetical study of the colonies indicated chromosome abnormalities identical to those in the patients 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.

Molecular cloning and expression of mouse homologue of SFA-1/PETA-3 (CD151), a member of the transmembrane 4 superfamily

We have isolated mouse SFA-1 (CD151) cDNA from a mouse myelomonocytic leukemia cell line, WEHI-3. Mouse CD151 mRNA comprises approximately 1.8 kb, has 253 amino acid residues with 93% identity to human CD151 and contains four putative transmembrane domains, a number of cysteine residues and one potential N-glycosylation site located at a site corresponding to that in human CD151. Mouse CD151 gene expression was observed in many cell types, but was either absent or present at a low level in brain and lymphoid cells and tissues, including thymus and spleen. The expression patterns of mouse and human CD151 genes are similar.

Adult T cell leukemia associated with eosinophilia: analysis of eosinophil-stimulating factors produced by leukemic cells.

The mechanism of eosinophilia in a patient with adult T cell leukemia (ATL) was investigated. A 61-year-old woman with ATL presented marked eosinophilia. No parasite infections or allergic diseases were found in this patient. The number of eosinophils fluctuated in parallel with that of ATL cells during her clinical course. The patients serum and the culture supernatant of ATL cells showed eosinophil colony-stimulating activity. Northern blot analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5), which are known eosinophil CSFs, showed that only GM-CSF but not IL-3 or IL-5 was expressed in freshly separated and cultured ATL cells. Since neutrophil and monocyte numbers did not increase, it is suggested that GM-CSF and unknown cytokines other than IL-3 and IL-5 produced by ATL cells synergistically stimulated eosinophil precursors in the present case.

MOLECULAR CLONING OF THE CDNA ENCODING A + U-RICH ELEMENT RNA BINDING FACTOR

Using the differential display method, a new cDNA clone, termed laAUF1, encoding the human A + U-rich RNA-binding motif was isolated and sequenced. Analysis of the protein sequence of laAUF1 indicates 73% homology between the deduced polypeptide sequences of laAUF1 and AUF1 in the region encoding a consensus motif for two non-identical RNA recognition motifs (RRMs) and Gln-rich motif. We suggest that the similar affinities of laAUF1 and AUF1 for particular A + U-rich elements (ARE) sequences are related to their potencies as mRNA destabilizers.

ENHANCEMENT OF MDR1 GENE EXPRESSION BY TRANSFORMING GROWTH FACTOR-BETA 1 IN THE NEW ADRIAMYCIN-RESISTANT HUMAN LEUKEMIA CELL LINE ME-F2/ADM

894 leukemia treated with interferon-a. Leukemia 1996; 10: 1134– growth-regulating cytokines and receptors. Recently, Beelen 1138. et al demonstrated that IFN affects hematopoietic recovery 2 Guilhot F, Guerci A, Fiere D, Harrousseau JL, Maloisel F, Bouabafter allogeneic bone marrow transplantation. This finding dallah R, Guyotat D, Rochant H, Najman A, Nicolini F, Colombat together with the documented in vitro properties of IFN on Ph, Abgrall JF, Ifrah N, Briere J, Bauters F, Navarro M, Morice P, marrow stroma cells raises the question of whether prolonged Bordessoul D, Vilques JP, Desablens B, Tertian G, Blanc M, Chastreatment with IFN may result in lasting or irreversible tang C, Tanzer J. The treatment of chronic myelogenous leukemia alterations of the marrow microenvironment leading to by interferon and cytosine-arabinoside: rational and design of the French trials. Bone Marrow Transplant 1996; 17 (Suppl 3): 29–31. myelodysplasia. 3 Sacchi S, Kantarjian H, O’Brien S, Cohen PR, Pierce S, Talpaz M. The finding of aberrant cytogenetic evolution in CML under Immune-mediated and unusual complications during interferonIFN therapy appears to be a major problem and requires alfa therapy in chronic myelogenous leukemia. Blood 1995; 13: further investigation on a larger series to elucidate the underly2401–2407. ing mechanisms and evaluate the influence of such chromo4 Peschel C, Aman MJ, Rudolf G, Aulitzky WE, Huber C. Regulation somic aberration on CML evolution especially in chronic of the cytokine network by interferon: a potential mechanism of phase. interferon in chronic myelogenous leukemia. Semin Hematol 1993; 30 (Suppl 3): 28–31. 5 Beelen DW, Graeven U, Elmaagacli AH, Niederle N, Kloke O, F Maloisel Service d’Onco-Hématologie Opalka B, Schaefer UW. Prolonged administration of interferon-a A Laplace and Laboratoire de Cytogenetique in patients with chronic-phase Philadelphia chromosome-positive F Uettwiller Hôpitaux Universitaires de Strasbourg chronic myelogenous leukemia before allogeneic bone marrow B Lioure 67098 Strasbourg cédex, France transplantation may adversely affect transplant outcome. Blood F Oberling 1995; 85: 2981–2990.

Translocation t(1;3)(p36;q21) in Sideroblastic Anaemia

An unique case of primary acquired sideroblastic anaemia (PASA) with hyperactive thrombopoiesis is described. Chromosome study revealed that the bone marrow cells of the affected patient contained t(1;3)(p36;q21). A prominent feature was marked megakaryocytic hyperplasia with dysmegakaryocytopoiesis. The platelet count temporarily exceeded 500 x 10(9)/1. In addition, we studied the cellular distribution of the unusual chromosome abnormality in this case. Few erythroid colonies (CFU-E and BFU-E) were observed and normal numbers of CFU-GM were formed. Some metaphases containing the clonal karyotypic abnormality were found in the granulocyte-macrophage colonies. However, no abnormal metaphases were apparent in preparations of T and B lymphocytes. The findings in the present case suggest that the long arm of chromosome 3 may contain a region involved in the regulation of megakaryopoiesis. Furthermore, our results strongly indicate that the target cell for chromosomal change is not a pluripotent stem cell (common to lymphoid and myeloid cells) but a progenitor cell common to all myeloid lineages.

Immunological Analysis of T Cells Bearing T Cell Receptor α/β or γ/δ in Patients with Granular Lymphocyte Proliferative Disorder

Immunological analysis of 2 cases of granular lymphocyte proliferative disorder with clonal expansion of CD3+4”8+ T cells bearing either T cell receptor α/β (patient 1) or T cell receptor γ/δ (patient 2) is reported. Significant cyto-toxic activity against K562 was observed in peripheral blood mononuclear cells (PBMC) isolated from patient 2, but not in PBMC from patient 1, although the cytotoxic activity of patient 1 could be augmented following incubation with anti-CD3 monoclonal antibody (MoAb). Northern blot analysis revealed that perforin mRNA was expressed in both patients. Proliferative response to phy-tohemagglutinin, anti-CD3 MoAb and 12-0-tetradecanoylphorbol-13-acetate was low in PBMC from both patients compared to that from healthy controls. Cytoplasmic free calcium of PBMC from the 2 patients increased similarly to that of healthy controls after treatment with anti-CD3 MoAb.

Evidence for the Neoplastic Involvement of Monocytic, Eosinophilic and Basophilic Lineages in Acute Myelomonocytic Leukemia with Eosinophilia

To investigate the origin of cells observed in acute myelomonocytic leukemia with eosinophilia (M4E0), we carried out morphological and cytogenetic studies of colonies derived from leukemic precursors. Marrow cells from a patient with M4E0 at second relapse revealed an abnormal karyotype; 47,XY, +8, inv(16)(p13q22), 17p-. Cytogenetic studies of leukemic colonies showed the same karyotypic abnormality. The primary and secondary colonies consisted of monocytes, eosinophils and basophils. These results indicated that the neoplastic process in this patient originated in a stem cell capable of differentiation into at least monocytes, eosinophils and basophils.

Simultaneous establishment of myeloid and B‐lymphoid cell lines with identical chromosome abnormalities from Philadelphia chromosome‐positive chronic myelogenous leukaemia

Summary. Two continuously growing cell lines, designated YOS‐M and YOS‐B, were established simultaneously from a patient with Philadelphia (Ph1) chromosome‐positive chronic myelogenous leukaemia (CML) in myeloid blast crisis. Both YOS‐M and YOS‐B had the Ph1 chromosome and identical additional chromosome abnormalities, which were not detected in the chronic phase. Cytochemical analysis showed that YOS‐M was significantly positive for peroxidase, whereas YOS‐B was entirely negative. YOS‐M expressed myeloid‐associated antigens (CD14, CD33) as well as CD4, CD25 and CD34. The surface phenotype of YOS‐M was identical to that of the leukaemic blasts found in the patient. On the other hand, YOS‐B expressed mature B‐cell markers, CD19, CD20, CD21 and surface immunoglobulin, but not myeloid‐associated antigens. These two cell lines showed an identical rearrangement pattern of the break point cluster region on chromosome 22, but rearrangement of the immunoglobulin heavy chain gene was detected only in YOS‐B. These findings provide definite evidence that CML cells still have the capability to differentiate and mature along different haematopoietic cell lineages even after blast crisis.

Interleukin-4 in chronic myelomonocytic leukemia. Growth suppression of hematopoietic precursors in the chronic phase and stimulation in the acute phase.

We examined the effects of interleukin-4 (IL-4) on the growth of hematopoietic precursors from a patient with chronic myelomonocytic leukemia (CMMoL). In the chronic phase of the disease, IL-4 inhibited spontaneous colony formation by CMMoL cells in semi-solid culture. However, in the acute phase, IL-4 promoted colony formation. These effects of IL-4 were abolished completely by the addition of anti-IL-4 neutralizing antibodies. The spontaneous colony formation by CMMoL cells in both the chronic and acute phases was inhibited by the addition of anti-IL-6 antibodies. On the other hand, neither anti-IL-6, anti-granulocyte macrophage colony-stimulating factor (GM-CSF), anti-IL-1 beta nor anti-tumor necrosis factor alpha (TNF alpha) antibodies inhibited IL-4-induced colony formation by CMMoL cells in the acute phase. IL-4 suppressed the production of IL-6 by CMMoL cells in both the chronic and acute phases. These results suggest that in the present patient, IL-4 suppressed the IL-6-mediated autocrine growth of CMMoL cells in both the chronic and acute phases, but directly stimulated their growth in the acute phase.