Preferred co-localization of chromosome 8 and 21 in myeloid bone marrow cells detected by three dimensional molecular cytogenetics.

The impact of chromosome architecture in the formation of chromosome aberrations is a recent finding of interphase directed molecular cytogenetic studies. Also positive correlation of translocation frequencies and spatial proximity of chromosomes was described. Thus, disease specific chromosomal translocations could be due to tissue specific genomic organization. However, no three-dimensional interphase fluorescence in situ hybridization (FISH) studies for the nuclear architecture of bone marrow (BM) cells have previously been done. In this study, BM of three secondary acute myelogenous leukemia (AML) cases with trisomy 8 and otherwise normal karyotype were evaluated. Bone marrow cells of one AML and one ALL (acute lymphoblastic leukemia) case, peripheral blood lymphocytes and human sperm, all of them with normal karyotype, served as controls. Multicolor banding (MCB) probes for chromosomes 8 and 21 were applied in suspension-FISH (S-FISH). Interestingly, in myeloid bone marrow cells chromosomes 8 (di- and trisomic) and 21 tended to co-localize with their homologue chromosome(s), rather than to be separated. Thus, the co-localization of chromosomes 8 and 21 might promote a translocation providing a selective advantage of t(8;21) cells in AML-M2. In summary, the concept that tissue specific spatial proximity of chromosomes leads to enhanced translocation frequencies was further supported.

Delineation of yet unknown cryptic subtelomere aberrations in 50% of acute myeloid leukemia with normal GTG-banding karyotype.

Acute myeloid leukemia (AML) is a heterogeneous disease with respect to clinical prognosis and acquired chromosomal aberrations. After routine banding cytogenetic analysis 45% of AML patients show a normal karyotype (NK-AML). For a better understanding of development and progression in AML, it is important to find markers which could be primary genetic aberrations. Therefore, in this study 31 patients with NK-AML were analyzed by new high resolution molecular cytogenetic approaches. A combination of multitude multicolor banding and metaphase microdissection-based comparative genomic hybridization revealed deletions of the subtelomeric regions in 6% of the studied cases. According to these results, locus-specific probes for the subtelomeric regions of chromosomes 5, 9, 11, 12 and 13 were applied on 22 of the studied 31 NK-AML cases. Surprisingly, 50% of them showed deletions or duplications. These aberrations occurred in the in vitro proliferating as well as in the non-proliferating cells. Meta-analysis of the aberrant regions revealed that they often include genes known to be associated with tumors, e.g. RASA3 on chromosome 13. These results implicate that aberrations in the subtelomeric regions of NK-AML occur quite often and may be considered as primary genetic changes, and should not be neglected in future diagnostic approaches.

[A rare cause of anemia in a kidney-transplant recipient]. / Seltene Ursache einer Anämie bei einer nierentransplantierten Patientin.

BACKGROUND: Anemia is a phenomenon frequently observed after kidney transplantation and differential diagnosis is broad. CASE REPORT: A 39-year-old woman who had been transplanted a kidney of her father 11 months ago was admitted to the hospital because of severe and worsening anemia (hematocrit [Hct] 0.24). She was under a standard posttransplant immunosuppressive protocol consisting of tacrolimus, mycophenolate mofetil (MMF) and prednisolone. Kidney function was excellent (serum creatinine 118 micromol/l), clinical symptoms of anemia included vertigo, fatigue and low blood pressure. Striking laboratory features were reticulocytopenia (1 per thousand), high ferritin (3,486 microg/l) and low folic acid (4.8 nmol/l), other parameters remained in the normal or therapeutic range. Endoscopic examinations did not reveal any pathologic finding. Bone marrow biopsy, however, showed giant pronormoblasts and the missing of more mature forms as a possible hint to a lack of, e. g., vitamin B(12) (whose serum level was normal, though). After all, the most probable cause of the anemia seemed to be a toxic drug effect and MMF as a possible causative agent was significantly reduced. Nonetheless, the red blood cell count continued to fall (lowest Hct 0.18). On a later outpatient visit all of a sudden positive IgM and IgG antibodies against parvovirus B19 could be detected. Due to a high virus load short-term immunoglobulin treatment was instituted, after which Hct levels rose to normal and virus load decreased to a low degree although still detectable. CONCLUSION: An infection with parvovirus B19 should always be taken into account as a possible cause of anemia in immunosuppressed patients. Establishing the diagnosis in the acute stage of the disease can be difficult, as antibodies are often negative in these patients and viremia remains the only proof. In most cases a substantial reduction of immunosuppressive therapy is necessary, the infection's relevance for the development of a potentially life-threatening myocarditis is still a matter of debate.

Thrombocytopenic purpura in a patient with macrolide-treated upper airway infection - drug related side effect or idiopathic thrombocytopenic purpura (ITP)

Os autores apresentam relato de caso de um homem de 55 anos de idade que desenvolveu púrpura trombocitopênica com sangramento da pele e membranas mucosas e macro-hematúria após infecçäo das vias aéreas superiores tratada com o macrolídeo roxitromicina. Foi feito o diagnóstico de púrpura trombocitopênica idiopática crônica com início agudo e excluído o de citopenia droga-induzida devido ao rápido início após ingestäo de apenas três comprimidos, à recuperaçäo retardada, ao curso crônico e aos dados epidemiológicos. O diagnóstico deferencial e o tratamento säo discutidos resumidamente