Ritsuko Yoshioka

X-Linked Syndrome of Polyendocrinopathy, Immune Dysfunction, and Diarrhea Maps to Xp11.23-Xq13.3

We describe genetic analysis of a large pedigree with an X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea (XPID), which frequently results in death during infancy or childhood. Linkage analysis mapped the XPID gene to a 17-cM interval defined by markers DXS8083 and DXS8107 on the X chromosome, at Xp11. 23-Xq13.3. The maximum LOD score was 3.99 (recombination fraction0) at DXS1235. Because this interval also harbors the gene for Wiskott-Aldrich syndrome (WAS), we investigated mutations in the WASP gene, as the molecular basis of XPID. Northern blot analysis detected the same relative amount and the same-sized WASP message in patients with XPID and in a control. Analysis of the WASP coding sequence, an alternate promoter, and an untranslated upstream first exon was carried out, and no mutations were found in patients with XPID. A C-->T transition within the alternate translation start site cosegregated with the XPID phenotype in this family; however, the same transition site was detected in a normal control male. We conclude that XPID maps to Xp11.23-Xq13.3 and that mutations of WASP are not associated with XPID.

Interleukin-7 (IL-7)-induced proliferation of CD8+ T-chronic lymphocytic leukemia cells

Interleukin-7 (IL-7) is a growth factor for pro-B cells, pre-B cells, and thymocytes and is known to induce the proliferation of normal human peripheral T cells. Moreover, human B and T acute leukemia cells with immature surface markers proliferate in response to IL-7. Here we describe a case of T-chronic lymphocytic leukemia, in which the leukemic cells showed a proliferative response to human recombinant IL-7in vitro. The patient was a 74-year-old woman with anemia and thrombocytopenia, whose bone marrow was fibrosed and infiltrated with pathologic cells. Surface markers of the leukemic cells were CD2(+), CD3(+), CD5(+), CD7(+), CD8(+), and CD4(−). Both T-cell receptor β-chain and γ-chain genes were found to be rearranged by immunogenotypic analysis. The leukemic cells proliferated in response to IL-7 dose dependently. The DNA synthesis of CLL cells was stimulated by not only IL-7 but also IL-2 and IL-4. The IL-7-induced proliferation was not inhibited by antibodies to IL-2 receptors or the anti-IL-4 antibody. These findings indicate that IL-7 may induce the proliferation of peripheral CD8+ T cells, even on its pathological counterpart.

Aggressive natural killer cell lymphoproliferative disorder associated with Epstein-Barr viral RNA.

Lymphoproliferative disorder of natural killer cells is a heterogeneous disorder, and an association with Epstein‐Barr virus (EBV) is suggested in some cases. A Japanese male presenting with recurrent nasopharyngeal problems developed fever, generalized lymphadenopathy, and hepatosplenomegaly. Separated cells from lymph nodes were shown to have a natural killer (NK) cell, CD2(+), CD3(−), CD16(+), CD56(+), HLA‐DR(+) phenotype. A progressive abnormality of hepatic function was associated with hepatorenal failure and death. A serologic study suggested reactivated EBV infection. In situ hybridization (ISH) studies showed Epstein‐Barr virus‐encoded RNA (EBER)‐1 in lymph nodes, with lymphocytes infiltrating the liver and tissue from ethmoid sinus surgery 3 years prior to development of obvious lymphoproliferative disease. Polymerase chain reaction performed on lymph node DNA, using oligonucleotide primers specific for the EBV lymphocyte‐determined membrane antigen (LYDMA) gene, revealed a single band, suggesting monoclonal proliferation of the tumor. NK activities of the lymphocytes from the lymph node and peripheral blood were markedly decreased. These findings suggest a close relationship between EBV infection and development of NK cell lymphoproliferative disorder. Am. J. Hematol. 54:314–320, 1997.

Electron microscopic morphometry of chronic type lymphoid leukemias

Malignant cells from 1 case of chronic lymphocytic leukemia of the T-cell type (T-CLL), 5 cases of chronic lymphocytic leukemia of the B-cell type (B-CLL), 1 case of prolymphocytic leukemia of the B-cell type (B-PLL), 1 case of lymphocytic lymphoma of intermediate differentiation of the B-cell type (B-ILL), 1 case of splenic B-cell lymphoma with circulating villous lymphocytes (SLVL), and 2 cases of hairy cell leukemia (HCL) were measured on electron micrographs. The area of the cytoplasm, nucleus, nucleoli, and the perimeters of nuclei were measured and the nucleo-cytoplasmic ratio, nucleolo-nuclear ratio, and nuclear contour index (NCI) were calculated. Malignant cells from B-PLL had the largest cytoplasmic, nuclear, and nucleolar areas. The NCI was largest (4.74) in T-CLL. B-ILL, B-PLL, and SLVL had an intermediate (4.5) NCI. HCL and B-CLL had the smallest (4.1) NCI. Lymphoid cells in SLVL were smaller in size than HCL cells and had a higher NCI than that of HCL. Thus, electron microscopic morphometry can provide further information to aid in distinguishing chronic type lymphoid leukemias.

Light and electron microscopic study of vacuolated cells in immunoblastic lymphadenopathy-like T-cell lymphoma

Three cases of immunoblastic lymphadenopathy (IBL)‐like T‐cell lymphoma were analyzed immunologically, and the ultrastructure of mononuclear cells in the lymph nodes and peripheral blood was examined. In the peripheral blood, light microscopic examination revealed vacuolated lymphocytes. These vacuolated lymphocytes formed rosettes with sheep erythrocytes, and they were CD3‐ and CD4‐positive using the avidin‐biotin method in cases 1 and 2. Electron microscopic examination revealed two kinds of abnormal lymphocytes. One kind was of B‐cell nature with rich lamellated rough‐surfaced endoplasmic reticulum and mitochondria. The other kind had a large cytoplasm, in which Golgi apparatus, some endoplasmic reticulum, some mitochondria and a few vacuoles were seen. Some of these vacuoles had remnants of mitochondrial cristae or were enlarged endoplasmic reticulum. The vacuolated T lymphocytes and activated lymphocytes of B‐cell nature disappeared with chemotherapy but reappeared with relapse of the disease. These observations suggest that vacuolated cells are related to pale cells in lymph node sections. In other words when these vacuolated cells are found in the peripheral blood of patients with lymphoid malignancies, IBL‐like T‐cell lymphoma can be suspected.