1. Genomic instability in bone marrow failure syndromes
http://www3.interscience.wiley.com/c...TRY=1&SRETRY=0
FISH more sensitive than conventional cytogenetics, Monosomy 7 carries poor prognosis, Trisomy 8 good prognosis. Trisomy 8 which develops in AA patients (start as AA and evolve into MDS after Trisomy 8 is discovered) has a better prognosis than primary MDS with Trisomy 8
Patient # 13 evolved from normal cytogenetics to 50% Trisomy 8, but the initial marrow was analysed only with conventional cytogenetics
2. Clinical relevance of cytogenetic abnormalities at diagnosis of acquired aplastic anaemia in adults.
http://pt.wkhealth.com/pt/re/bjha/ab...195628!8091!-1
3. Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia
http://bloodjournal.hematologylibrar...full/99/9/3129
full text available online
Trisomy 8 is found in more advanced FAB subtypes, often included in the intermediate-risk group with average survival of 2.4 years (17.2 months in an analysis of 115 patients with trisomy)8,26 and time to evolution of AML of 1.6 years.18 The sharp contrast of this observation with the clinical course and prognosis of trisomy 8 evolving from AA suggests a different biology for an apparently identical cytogenetic abnormality in late AA and in primary MDS.
Monosomy 7 should continue to be regarded as itself a dire event, but for trisomy 8, the cytogenetic abnormality does not alter the desirability of an aggressive immunologic approach to improve the function of an empty BM.
4. Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome
http://www.pubmedcentral.nih.gov/art...?artid=1895154
full text online
IST improves bone marrow function in selected patients with MDS, though it does not generally eliminate the cytogenetically abnormal clone.37 Patients who are younger, are HLA DR15 positive, and have more recent onset of disease have a high response rate.22 This high-responder group includes most patients with trisomy 8 (E.M.S., unpublished data, 2005).
In our experiments, clonally expanded CD8 cells showed apparent cytotoxicity specifically for autologous trisomy 8 hematopoietic progenitors. MDS with 5q– and monosomy 7 have neither skewing of the T-cell repertoire nor T-cell effector cytotoxicity for karyotypically abnormal progenitors. Intrinsic sensitivity of trisomy 8 cells to lymphocytes of their cytokine products, while not rigorously excluded, seems unlikely because of the following: (1) alloactivated T lymphocytes do not produce the same effect as autologous T cells; (2) adding interferon-γ (IFN-γ) to cell culture did not decrease the proportion of trisomy 8 cells (data not shown); (3) Fas antagonist did not preferentially conserve trisomy 8 cells in CD3-depleted marrow; (4) lymphocytes from patients on CsA therapy did not diminish the proportion of trisomy 8 cells; and (5) there was a reciprocal relationship between trisomy 8 clone expansion after IST and trisomy 8–specific T-cell reduction.
An immunologic description of the pathophysiology of trisomy 8 MDS must also explain the myelosuppression encountered in this condition. During the immune response to trisomy 8 cells, normal hematopoietic cells could be damaged as “bystanders,” leading to generalized hematopoietic cell destruction and pancytopenia. Such a bystander effect has been described in a mouse model of immune-mediated marrow failure46: donor lymphocytes, activated in response to H2 differences in an F1 hybrid recipient, were cytotoxic to hematopoietic stem cells genetically matched at H2 to the effector cells. Bystander killing may result from cytokines released by activated T cells47 or by the cross-recognition of targets through molecular mimicry or epitope spreading.48-50
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