Aceruloplasminemia is an autosomal recessive disease of iron overload associated with mutation(s) in the ceruloplasmin gene. We report here a new case of aceruloplasminemia in a woman who is a ...compound heterozygote for two new mutations. Besides this novel genotypic profile, this observation provides new insights on: (i) iron metabolism with normal erythroid repartition, in the absence of serum non-transferrin-bound iron and with an increase of
59Fe plasma clearance; (ii) hepatic abnormalities associated with the presence of iron-free foci; (iii) the therapeutic management of the disease, chronic subcutaneous infusion of deferrioxamine being remarkably effective at reducing hepatic iron overload.
Deletion of the long arm of chromosome 20 is a recurrent abnormality observed in myelodysplastic syndromes (MDS) and in Philadelphia-chromosome-negative myeloproliferative disorders (MPD). Our ...objective was to characterize the deletion size among 38 MDS and MPD patients using fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) probes and to define commonly deleted and retained regions on chromosome 20. Patients were distributed in three groups according to the World Health Organization classification: MDS (22 patients), MPD (12 patients) and myelodysplastic/myeloproliferative diseases (four patients). FISH with centromeric, subtelomeric, and unique sequence probes was performed to characterize the deletion whereas its size was delineated using BAC clones. All 38 deletions were found to be interstitial. A commonly deleted region was identified for each of the three groups; it varied from 6.62 to 10.4 Mb and showed considerable overlapping. Two commonly retained regions (CRR), also showing overlapping, were identified in all three groups, one in the centromeric region, the other in the telomeric region. The deletion size is highly variable, with no apparent recurrent breakpoint. The deletion may result in the loss of one or several tumor suppressor genes but the target genes remain unknown. Loss of genes plays an important part in the myeloid leukemic process associated with del(20q). However, genes located in the retained chromosomal regions may also play a role in the oncogenetic mechanisms.
Multiple myeloma (MM) is a malignancy of the terminally-differentiated B cells and accounts for 10% of all hematological malignancies.
Chromosome 1 aberrations are frequently described, the short arm ...being preferentially involved in deletions and the long arm
in gains. The abnormalities were identified in the bone marrow of 37 MM patients by conventional cytogenetics. Fluorescence
in situ hybridization (FISH) was used to confirm the presence of the abnormalities and to better characterize them. Chromosome
1 abnormalities were grouped into 4 categories: balanced translocations, deletions, amplifications and jumping translocations
(JT). Breakpoints involved in balanced translocations were randomly distributed. The smallest region of overlap for deletions
was 1p11â1p21 (present in 27% of the patients) and for gains 1q31â1qter (present in 54% of the patients). The whole long arm
was found to be the donor segment for the majority of patients with JT, the most frequent recipients being chromosomes 16
and 19. Our results share some similarities with those obtained for 143 published patients studied by FISH. Band 1p21 was
found to be frequently deleted, leading to the assumption that a 1p deletion could lead to hemizygosity of at least 1 tumor
suppressor gene. Two regions of 1q showed preferential gains: q12 to q22 and q31 to q42; these amplifications could induce
the overexpression of 1 or more oncogenes. In conclusion, our results confirm that chromosome 1 abnormalities play an important
role in the pathogenesis of multiple myeloma.
Rearrangements involving the IGH gene have been identified in about 50% of non-Hodgkin's B-cell lymphomas (NHL) and correlated
to clinical relevant subgroups. However, the detection rate varied ...greatly with the technique used. The incidence of IGH rearrangements
was analyzed using several fluorescence in situ hybridization (FISH) techniques on metaphases obtained from 57 patients with
nodal NHL. An IGH rearrangement was identified in 42 cases (73.7%). A t(14;18)(q32;q21) was found in 17 of the 20 follicular
lymphomas (85%) studied and a t(11;14)(q13;q32) in 10 of the 11 mantle cell lymphomas (91%). IGH rearrangements were identified
in 12 of the 26 diffuse large B-cell lymphomas (46%), including 5 t(14;18)(q32;q21) and 2 t(3;14)(q27;q32). Conventional cytogenetics
was uninformative in several cases. However, the complemented analysis using Multi-FISH and/or chromosomal whole paint enabled
the characterization of complex IGH translocations in follicular lymphomas and mantle cell lymphomas and the identification
of all the chromosomal partners involved in the IGH rearrangement in diffuse large B-cell lymphomas. This study shows the
interest of using metaphase FISH in addition to conventional cytogenetics. Following banding techniques, FISH with the IGH
dual color probe could be the first approach in NHL, after which chromosome painting and M-FISH could be used to identify
the chromosomal partner involved in the IGH rearrangement.
Background: Several attempts have been made to determine whether interphase fluorescence in situ hybridization (I-FISH) on
bone marrow or peripheral blood specimens is a good alternative to ...conventional cytogenetics (CC) in calculating the residual
proportion of Philadelphia (Ph) chromosome-positive cells during treatment follow-up of patients with chronic myeloid leukemia.
Materials and Methods: Nineteen patients were selected for I-FISH follow-up compared to CC. All samples were also classified
into 4 groups according to the percentage of residual Ph chromosome-positive metaphases analyzed in CC. I-FISH was performed
using the LSI bcr/abl dual ES color probe (Vysis®). Results: A high correlation was observed between the frequency of Ph chromosome-positive
cells, assessed by CC and I-FISH (p<0.001). A high correlation was found between CC and I-FISH for 12 patients, but not for
the remaining 7. Applying the same classification for I-FISH did not show a good relationship between the two techniques (p<0.001).
Conclusion: Dual color I-FISH is a reliable method to monitor the size of the Ph chromosome-positive clone in bone marrow
of treated CML patients. However, it has to be complementary to conventional cytogenetics because it cannot detect the emergence
of other chromosomal abnormalities in Ph chromosome-positive or -negative cells.
Chronic myelogenous leukemia has a poor outcome when treated with hydroxyurea or busulfan. These agents can control the disease, but they do not eliminate Philadelphia chromosome–positive stem cells ...from the bone marrow. Allogeneic bone marrow transplantation, considered to be the only curative treatment, prolongs survival in up to 70 percent of a small subgroup of young patients.
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An antileukemic effect of interferon alfa has been demonstrated and cytogenetic responses (the reduction or elimination of Philadelphia chromosome–positive cells in the marrow) have been reported in patients with chronic myelogenous leukemia.
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Three randomized clinical trials comparing interferon alfa with conventional chemotherapy . . .
The use of new nuclei probes in fluorescent in situ hybridization (FISH) at diagnosis and during follow up has recently allowed the detection of a deletion of the 5′abl region on the derivative ...chromosome 9 among some CML patients. This deletion seems to be a powerful and independent prognostic factor. The aim of our study was not only to estimate the frequency of the deletion of the 5′abl region among chronic myeloid leukemia (CML) patients with bcr-abl fusion gene, but also, to assess whether this deletion is concomitant with the formation of the Philadelphia (Ph) chromosome or represents a sign for progression of the disease, and finally to evaluate the prognostic implications of this abnormality. One hundred and twelve patients were analysed using FISH with LSI bcr-abl dual ES color probes, at the moment of the diagnosis when possible or, if not, on a sample with a strong rate of Ph+ metaphases evaluated by conventional cytogenetics. When the deletion was highlighted in a patient, we performed an hybridization on all the samples available during the follow-up. The deletion of the 5′ region of the gene abl was detected among 9 patients. When the deletion was found in a patient, it was present in all the Ph+ metaphases and nuclei and in all the samples studied at diagnosis and during follow up. In these patients, we never identified cells carrying the Ph chromosome translocation without the deletion. None of the patients with the deletion had a major cytogenetic response to treatment with interferon. The deletion of the 5′abl region on der(9), present in approximately 9% of the CML, takes place at the same time as the formation of the Ph chromosome translocation and seems of worse prognosis. The detection of this deletion could thus constitute an argument to start STI treatment in first intent for these patients.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Philadelphia (Ph) chromosome, resulting from a t(9;22)(q34;q11), is one of the most frequent chromosomal abnormalities observed among patients with acute lymphoblastic leukemia (ALL). Main of ...study: To analyze the distribution of Ph chromosome-positive ALL patients.
Conventional cytogenetic analysis was performed on bone marrow cells at the time of diagnosis and/or relapse of 208 patients shown to have B-cell ALL. Fluorescent in situ hybridization studies using probe LSI BCR-ABL dual ES color (Abbott, Rungis, France) and other types of probes were performed on the available cytogenetic pellets.
Thirty-three Ph chromosome-positive ALL patients were identified between 1981 and 2008. The Ph chromosome was present in 39.7% of the patients older than 25 years, but in only 4.3% of the patients younger than 15 years. A pseudodiploid karyotype was found in 68.75% of the patients and hypodiploidy in a further 15.6% of the patients. FISH studies revealed the breakpoint to be located in the major breakpoint cluster region in 20% of the patients and in the minor in the remaining 80% of the patients. Complex rearrangements of the derivative chromosomes 9 or 22 were identified in four patients, including a complex Ph translocation, t(9;22;X).
Ph chromosome-positive ALL patients show cytogenetic characteristics that differ from those of other ALL patients.
Abstract Regulation of normal hematopoiesis by neuropeptide substance P (SP) and its amino terminal fragment, SP(1–4), has been reported. Endogenous erythroid colony (EEC) formation without ...erythropoietin is characteristic of polycythemia vera (PV), a chronic myeloproliferative disorder. We investigated the effect(s) of SP and SP(1–4) on EEC formation from PV BM mononuclear cells (BMMCs) and purified CD36+ erythroid progenitors. We found a potent in vitro inhibitory effect of SP and SP(1–4) on PV EEC formation for both BMMCs and CD36+ erythroid progenitors. The influence of SP and SP(1–4) on PV progenitor erythroid differentiation and cell viability was also investigated, and the impact of neurokinin receptors and G proteins in the inhibition were analyzed by quantitative PCR and with specific inhibitors. This progenitor inhibition was: (1) not mediated by accessory cells; (2) characterized by an increase in cell death and inhibition of the EPOindependent terminal erythroid differentiation; and (3) not mediated by the same neurokinin receptor. NK-1R and NK-2R antagonists completely abrogated the SP inhibitory effect but not SP(1–4)-induced inhibition. Furthermore, the truncated form of the NK-1R was predominant over the full-length mRNA and could mediated the SP inhibitory effect on PV CD36+ erythroid progenitors. Different G proteins were also implicated according to the erythroid differentiation stage of the PV cells. The observation of an inhibitory effect of SP and its related peptide, SP(1–4), on PV EEC formation at physiological concentrations (10–8 M) suggests that neuropeptides represent a way to downregulate pathologic expansion of PV progenitors.
Trisomy 15 as the sole autosomal anomaly is uncommon in hematological malignancies but could be preferentially associated with myelodysplasia. We report a 61-year-old man who developed pancytopenia ...following two courses of chemotherapy for chronic lymphoid leukemia. Cytogenetic studies at diagnosis of pancytopenia with R banding showed a 47,XY,+153/45,X3/46,XY14 karyotype. A review of the 53 cases of myelodysplastic syndromes (MDS) and myeloid related disorders associated with trisomy 15 reported in the literature showed that 18 of the 31 men also lost the Y chromosome in the trisomic 15 cell line. Their mean age was significantly higher than that of males who had not lost the Y chromosome (p <0.05). The main feature of the patient reported here is the presence of two abnormal cell lines, one having lost the Y chromosome, the other having gained a chromosome 15. Therefore, the two events occurred independently, the loss of the Y chromosome being possibly due to aging and the trisomy 15 to the hematologic disorder.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK