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Background: Besides peripheral cytopenias, bone marrow abnormalities, such as fibrosis, pure red cell aplasia and aplastic anemia have been reported in patients with systemic lupus erythematosus (SLE), suggesting that bone marrow may be a 25 target organ in SLE., Aim: Our objective was to describe this bone marrow involvement., Methods: This registry is a nationwide retrospective study. Centers provided data concerning medical history, SLE manifestations, type of hematologic disorder, treatments and outcome. Bone marrow aspirations and/or biopsies were transferred for centralized review., Results: Thirty patients from 19 centers were included. Central hematologic manifestations comprised bone marrow fibrosis (n = 17; 57%), pure red cell aplasia (n = 8; 27%), myelodysplastic syndrome (n = 3; 10%), aplastic anemia and agranulocytosis (n = 1; 3% each). Bone marrow involvement was diagnosed concomitantly with SLE in 12 patients. Bone marrow biopsies showed fibrosis in 19 cases, including one case of pure red cell aplasia and one case of agranulocytosis and variable global marrow cellularity. Treatments included corticosteroids (90%), hydroxychloroquine (87%), rituximab (33%), intravenous immunoglobulins (30%), mycophenolate mofetil (20%) and ciclosporine (20%). After a median follow-up of 27 months (range: 1-142), 24 patients manifested complete improvement. No patient died., Conclusions: This registry comprises the largest series of SLE patients with bone marrow involvement. It demonstrates the strong link between SLE and bone marrow fibrosis. Patients with atypical or refractory cytopenia associated with SLE should undergo bone marrow examination to enable appropriate, and often effective, treatment. Long-term prognosis is good., (© The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

The term "paraneoplastic neurologic disorders" refers to a group of syndromes mediated by immune responses triggered by tumors that express neuronal proteins or by immunological disturbances caused by the tumor. In most cases, limbic encephalitis is a disorder of adulthood, particularly in association with small-cell lung cancer or a testicular germ-cell tumor. The clinical picture of this disorder includes anxiety, depression, confusion, delirium, hallucinations, short-term memory loss and sometimes seizures. We report on 2 new pediatric cases from a single hospital: in the first case, limbic encephalitis revealed Hodgkin lymphoma; it heralded meningeal relapse of acute lymphoblastic leukemia in the other. Despite its extreme rarity, this syndrome is a possible diagnosis in childhood., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Congenital acute leukemia is a rare event, presenting usually as an aggressive disease with a poor prognosis. A differential diagnosis is the transient myeloproliferative disorder observed in Down syndrome. We describe the case of an apparently healthy newborn male child presenting with normal peripheral blood (PB) counts but with a blast population on differentials. The child's condition and the blast population remained unchanged during the first year of life., Methods: Bone marrow and PB were morphologically analyzed. Multiparametric flow cytometry was performed at the time of diagnosis and repeated at 1 year. These studies were completed by cytogenetic and molecular analyses., Results: Bone marrow contained 40% of undifferentiated blasts. Multiparametric flow cytometry showed low expression of CD38, HLA-DR, and CD33 markers. All other markers were negative. Constitutional and blast cell karyotypes were normal. Fluorescence in situ hybridization analysis showed no rearrangement. Molecular studies were negative. The blast percentage remained stable during several months. After 1 year, the PB counts showed thrombocytopenia, with an increase of blast cells exhibiting the same phenotype. Clinically, an enlarged spleen was found. The child did not respond to chemotherapy and only partially to gemtuzumab ozogamicin. A cord blood cell transplantation was finally performed. With a follow-up of 12 months, the child is doing well., Conclusions: To our knowledge, this is the first case of congenital acute leukemia with initially indolent course in a newborn without Down syndrome. This observation emphasizes the importance of a careful follow-up., (Copyright © 2010 International Clinical Cytometry Society.)

Excessive apoptosis is implicated in the pathogenesis of myelodysplastic syndromes (MDS). We assessed by flow cytometry the expression of several members of the Bcl-2 family in bone marrow mononuclear cells (BMMNC) of 168 MDS samples at diagnosis. The proteins studied were Bcl-2, Bcl-xL (anti-apoptotic), Bax, Bad, Bak, and Bcl-xS (pro-apoptotic). The percentage of BMMNC expressing Bcl-2 and Bcl-xL was higher in refractory anemia with excess of blasts (RAEB), RAEB in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMML) than in refractory anemia (RA) and RA with ringed sideroblasts (RAS). Conversely pro-apoptotic proteins Bad, Bak, and Bcl-xS were detected in a higher percentage of cells in RA and RAS. RA and RAS were associated with an increased Bcl-xS/Bcl-xL ratio. The expression of anti-apoptotic proteins was also correlated with that of CD34 and P170 and with the percentage of blast cells. Two-color analyses demonstrated that CD34 and Bcl-2 were usually expressed in the same cells. No significant correlation was found with cytogenetic abnormalities. Higher expression of pro-apoptotic Bcl-2-family proteins (Bak, Bad, Bcl-xS) and higher Bcl-xS/Bcl-xL ratio were associated with longer survival and decreased risk of leukemic transformation in univariate analysis, whereas expression of anti-apoptotic proteins was associated with decreased survival. Consequently Bcl-2 proteins expression was well correlated with the International Prognostic Scoring System (IPSS). Our data confirm that the control of apoptosis is deregulated in MDS cells. Moreover, the study of markers such as CD34 (or Bcl-2), Bcl-xL, and Bcl-xS provides additional prognostic information., (Copyright 2002 Wiley-Liss, Inc.)

The expression of Bcl-2 family proteins (Bcl-2, Bcl-X, Bcl-XL, Bcl-Xs, BAX, BAD, MCL-1) and of Interleukin-1 converting enzyme (ICE)-related proteins (ICE, CPP32, ICH- 1) was analyzed in acute leukemia cells by flow cytometry. Most proteins studied were detectable in cell lines such as KG1a, HL60, K562 (myeloblastic), REH, RAJI and MOLT4 (lymphoblastic) and VAL (B-cell lymphoma). However, BCL-Xs and BAK were weakly expressed in K562, as were Bcl-X, BAD and BAK in the VAL line. In acute myeloid leukemia (66 cases studied), the proteins were expressed in most cases in a high percentage of cells, especially BAX and CPP32, without correlation with hematological characteristics. However, Bcl-2 was expressed in a higher percentage of cells in FAB M1 and M5 cases, and in CD34-positive cases, whereas Bcl-Xs was more frequently expressed in M3 cases. No differences were observed regarding fluorescence intensity. Higher percentages of Bcl-2-positive cells were associated with low remission rate, while expression of Bcl-Xs was predictive of high remission rate. In acute lymphoblastic leukemia (36 cases), all proteins studied were expressed in a majority of cases. Bcl-Xs was more frequently detected in T-cell type, and was also associated with a higher remission rate. These results suggest that apoptosis-controlling proteins may have a role in the pathogenesis and response to therapy of acute leukemia.

Trisomy 12 is the most common cytogenetic abnormality in chronic lymphocytic leukaemia (CLL) and may be a prognostic indicator. In the present study, fluorescence in situ hybridization (FISH) is shown to be a method of choice for detection of trisomy 12 in interphase cells. Seventy-five cases of B-cell CLL were analysed with a chromosome 12 specific alpha satellite DNA probe and results compared with those from cytogenetic analysis. FISH showed the three hybridization spots characteristic of trisomy 12 in 32/75 patients (42.6%). Sixty-three patients were also studied by conventional cytogenetics: failure in 7 cases, normal karyotype in 28, trisomy 12 in 9 (14.3%) and in 19 cases abnormalities other than trisomy 12. In these same 63 patients, trisomy 12 was detected on 29 occasions by FISH (46%): in one case of failure by cytogenetic analysis, in 9 cases thought to have a normal karyotype, in 10 cases carrying abnormalities other than trisomy 12 and in all 9 cases showing trisomy 12 by conventional cytogenetic investigation. Correlation between trisomy 12 and the three stages of the Binet classification indicated an increasing proportion of trisomy 12 from stage A to stage C. It is concluded that fluorescence in situ hybridization is a powerful and sensitive technique for detection of trisomy 12 in CLL and although more cases will be required to confirm a correlation between the incidence of trisomy 12 and the stage of the disease, this link could be important from a prognostic point of view.

Variant translocations (2;18 and 18;22) are described in this review. The chromosomal and molecular findings of these translocation of BCL2 and their effect on possible BCL2 gene activation is discussed. Unanswered questions still remain and these include why this is so rare compared to the 25% incidence recorded for translocations in Burkitt's lymphoma. Further studies are obviously still needed in order to determine the true frequency of these findings and their distribution in the various B-cell disorders.

The chromosome constitutions of stimulated lymphocytes from 50 B-cell chronic lymphocytic leukemia patients were studied using different stimulation systems, i.e., TPA alone or associated with different cytokines. Adequate metaphases were obtained in 44 subjects (88%). Among 20 patients with abnormal karyotypes (45.5%), 7 had trisomy 12. The most frequent structural abnormality was a 14q+ resulting from translocations including one t(11;14) and two t(14;17), while deletions on the long arms of chromosomes 6 and 13 constituted a second common alteration. The most important finding in this series was the recurrence of a t(18;22) observed in two cases.

The authors describe three cases of refractory anaemia with an excess of myeloblasts in the bone marrow (RAEM), associated with pyoderma gangrenosum (PG) and vasculitis. The first patient was an 85-year old man whose RAEM had begun in 1979. In 1985, he developed pyoderma gangrenosum in the popliteal fossa and on the right heel. Histology confirmed the diagnosis. A direct immunofluorescence test on the biopsy specimen was negative. Apart from the haematological syndrome, there were no laboratory abnormalities. The cutaneous lesions disappeared after 7 weeks of treatment with prednisolone 20 mg per day. The blood disease remained unchanged. The second patient was a 71-year old woman with RAEM since 1982. In 1984, she presented with lesions of cutaneous vasculitis located on the anterior aspect of the upper third of her left leg. There was neither arthralgia nor fever, and no history of drug toxicity or infection. Beside RAEM, polyclonal hyperglobulinaemia was present. Histological examination of the skin showed evidence of vasculitis with fibrinoid necrosis of vascular walls and perivascular lympho-histiocytic infiltrate with granulocytes and slight leucocytoclasia. Direct immunofluorescence testing of the skin demonstrated intravascular complement deposits. There were no circulating immune complexes; measurements of complement and complement fractions gave normal values; no cryoglobulin was found. The cutaneous lesions recurred on two occasions in 6 months, although no drug toxicity or infection could be elicited and the haematological syndrome was unaffected. The third patient was a 67-year old man with RAEM since 1982. In 1983, an ulcero-necrotic lesion spontaneously developed on his right leg.(ABSTRACT TRUNCATED AT 250 WORDS)