Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia

Although KIT mutations are present in 20–25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.     

Ring chromosome 8 and translocation t(8;21) in a patient with acute myeloblastic leukemia

Recurrent translocation t(8;21)(q22;q22) acute myeloid leukemia (AML) is often associated with secondary chromosome changes of which the clinical significance is not clear since they do not seem to impair the prognosis. Uncommon chromosome changes may lead to the identification of leukemogenetic factors associated with t(8;21) since the AML1/RUNX1-ETO fusion gene resulting from the translocation is thought to be unable alone to induce leukemia. We here report a patient with AML, t(8;21) and ring chromosome 8 resulting in partial chromosome 8 deletion. Another patient with partial 8q deletion has been previously reported. It is suggested that more attention be paid to the genes located in distal 8q in relation to leukemogenesis.     

RAG-dependent recombination at cryptic RSSs within TEL-AML1 t(12;21)(p13;q22) chromosomal translocation region

The recombination activating gene (RAG) is a lymphoid-specific endonuclease involved in the V(D)J recombination. It has long been proposed that mis-targeting of RAG proteins is one of the factors contributing to lymphoid chromosomal translocation bearing authentic recombination signal sequences (RSSs) in immunoglobulin (Ig) and T cell receptor (TCR) gene loci or cryptic RSSs (cRSSs). However, it is unclear whether primary sequence-dependent targeting mistake involved in the chromosomal translocation bearing no Ig/TCR gene loci is mediated by RAG proteins. Using an extrachromosomal recombination assay, we found RAG-dependent recombination in the regions dense in breakpoints within TEL and AML1 gene loci related to acute lymphoid leukemia-associated t(12;21)(p13;q22) chromosomal translocation. Sequence analyses revealed several heptamer-like sequences located in the vicinity of RAG-dependent recombination sites. By chromatin immunoprecipitation (ChIP) and ligation-mediated PCR (LM-PCR) assays, we have shown that RAG proteins bind to and cleave the TEL translocation region dense in breakpoints. These results suggest that mis-targeting of RAG proteins to cRSSs within TEL and AML1 translocation regions might be responsible for the t(12;21)(p13;q22) chromosomal translocation not bearing Ig/TCR regions.     

Familial (11;21)(p13;q22)pat balanced reciprocal translocation in a female child with regression of milestones

The role of balanced translocations in the human morphogenesis is difficult to interpret. A balanced reciprocal translocation (BRT) was observed in a female child referred with a history of regression of milestones. The cytogenetic findings by GTG-banding and fluorescence in situ hybridization revealed a BRT involving chromosomes 11p and 21q, i.e. 46,XX, t(11;21)(p13;q22). The father was found to be a carrier of the same BRT. This is the first report of reciprocal translocation involving 11p and 21q. The possible reasons for the manifestation of clinical features in the proband due to inherited BRT are discussed.     

Complex translocation t(9;21)(9;22)(q12p13)(q12q11) in the family of a child with 9p trisomy syndrome

Summary Leukocyte peroxidase activity was estimated in 5 patients with the juvenile form of neuronal ceroid lipofuscinosis (Spielmeyer-Vogt's disease) and in 15 healthy controls. In contradiction to recent reports normal activity of p-phenylene diamine mediated peroxidase was found in the patients. The possible role of contamination of the white cell preparation with hemoglobin is discussed.     

A Turner patient with a 45,X,t(1;2) (q41;p11.2) karyotype

The most common chromosomal anomaly is 45,X in the Turner syndrome. In addition to this, anomaly, mosaicism such as structural 46,X,i(Xq), 46,X,del(Xp), 46,X,r(X), 46,X,t(X;Y) and numerical 46XO/46,XX/47XXX are seen rather frequently. An infant with the Turner syndrome was found to have a karyotype 45X,t(1;2) (q41;p16) using high resolution banding. Based on our knowledge, we present the first case of 45X,t(1;2) (q41;p11.2), a karyotype in Turner's syndrome in the literature.     

A new case of trisomy for the distal part of 13q due to maternal translocation,t(9;13)(p21;q21)

Summary The first child of a mother with a balanced translocation (9;13) revealed a trisomy for the distal third of 13q. Clinical signs were microcephaly, hemangiomata, long incurved eyelashes, strabismus, enlarged bridge of the nose, abnormally long philtrum, high-arched palate, low set ears, hexadactyly of the four extremities, umbilical and inguinal hernias, neonatal respiratory distress, psychomotor and growth retardation. The proband presented also male pseudohermaphroditism and trigonocephaly. This last trait is the object of a discussion in which cases of partial trisomy 13q cited in the literature are considered for study of the incidence of this dyscephaly in this particular syndrome.     

Novel variant Ph translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in chronic myeloid leukemia involving a one-step mechanism

Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of ABL1.     

A novel chromosomal abnormality t (9;14)(p24;q13) in B-acute lymphoblastic leukemia

Acute lymphoblastic leukemia is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. We describe the clinical, morphologic, immunophenotypic and cytogenetic findings in the case of a 26-year-old man with B-lymphoblastic leukemia. Surface marker analysis revealed that they are positive for CD markers CD10, CD19, CD13, CD34, CD45 and HLA-DR, but negative for CD20, CD33, CD117 and CD11C markers. Cytogenetic analysis established a novel translocation, t (9;14)(p24;q13). Apart from this, spectral karyotyping revealed an additional translocation, t (6p; 14q). This is the first documented case of B-lymphoblastic leukemia with concurrent occurrence of both abnormalities. Further studies are needed to understand the role of this abnormality in carcinogenesis.     

Partial trisomies 13 and 22 due to nondisjunction of a maternal reciprocal translocation,t(13;22)(q22;q11)

Summary A family is reported in which the propositus has an extra G-like chromosome with an unusual G-banding pattern. Cytogenetic family studies showed that the mother is a carrier of a balanced reciprocal translocation t(13;22), which does not affect the size and morphology of the chromosomes involved. The propositus has a 47,XY,+der(22),t(13;22)(q22;q11) karyotype and is therefore partially trisomic for the distal third of the long arm of chromosome 13 and for a very small part of chromosome 22. The clinical findings are presented and compared with those of other reported cases of partial trisomies 13 and 22.     

Abnormal localization of proto-oncogene c-ets 1 in acute leukemia with translocation t(1: 11)(q21: q23)

The chromosome localization of a 5.4 kb DNA genomic probe of proto-oncogene c-ets 1 has been analysed in an acute monocytic leukemia with t (1; 11) (q21; q23) translocation. The c-ets probe has been translocated onto the rearranged chromosome 1, suggesting the involvement of the proto-oncogene in leukemias with chromosome rearrangements at band 11 q23.     

Familial C/D translocation t(9;13)(9p23;13q21) in a male associated with recurrent abortion

Summary A familial reciprocal translocation, established by R-banding as t(9;13) (9p23; 13q21), is described in a phenotypically normal male carrier, whose father is also a balanced carrier and wife had four consecutive spontaneous abortions. The role of translocation in reproductive failure through production of chromosomally unbalanced gametes or by impairment of the spermatogenesis is briefly discussed.     

A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor

The majority of Ewing sarcomas and peripheral neuroectodermal tumors (PNET) that have been karyotyped contain a specific translocation, t(11;22)(q23;q11). We report here a second nonrandom translocation, der(16)t(1;16)(q21;q13), in 2 of 20 cases of Ewing sarcoma (seven previously unreported) and 2 of 7 cases of PNET (all previously unreported). All cases with this translocation also contained the t(11;22). Comparison of C-banding patterns in tumor and peripheral lymphocyte karyotypes in one case indicated that the likely breakpoints were 1q21 and 16q13. The presence of this translocation in cell lines will enable further investigation of the molecular events important in the pathogenesis of Ewing sarcoma and PNET.     

A new case of reciprocal translocation t(10;13)(q16;q21) diagnosed in an AI boar

A new case of reciprocal translocation t(10;13)(q16;q21) was detected in a hybrid boar (Large White x Pietrain x Duroc x Hampshire) from an artificial insemination (AI) station. Altogether, 258 sires of 4 pure breeds as well as hybrid lines and crossbreeds were investigated. The diagnosis was based on classical cytogenetic examination following the standard protocols of lymphocyte cultures, Giemsa staining and G-, C- and Ag-I banding techniques. The population screening performed was an initial part of a long-term karyotype control system of boars kept at AI stations, which was started by the National Research Institute of Animal Production in Poland in 2007.     

A case of chronic myeloid leukemia with a translocation (12;22)(p13;q11)

Summary Chromosomal studies of the bone marrow and cultured peripheral blood cells in a 42-year-old female with the clinical and laboratory features typical for CML revealed a previously undescribed variant translocation involving chromosomes 12 and 22.