Vesna Djordjevic

Pattern of trisomy 1q in hematological malignancies: a single institution experience

An extra copy of 1q usually originates from the translocated unbalanced derivative chromosome, isochromosome, or jumping translocation. We report a pattern of partial trisomies and unbalanced whole-arm translocations of 1q in 10 patients: 5 with myelodysplastic syndrome, 3 with acute myeloid leukemia, and a single patient with acute lymphoblastic leukemia and myeloproliferative syndrome. The trisomy of 1q was registered as the sole karyotype aberration in one patient, while it was accompanied by a limited number of additional chromosomal changes in nine patients. These patients are a subset of a larger group of 92 adults carrying a wide variety of chromosome 1 anomalies within a complex cytogenetic context observed over a period between 1994 and 2006 in a panel of 3,786 hematologic patients at the Institute of Hematology in Belgrade. Conventional cytogenetics was supplemented by fluorescence in situ hybridization with a probe specific for the paracentric region of 1q. Whole-arm 1q translocations involved chromosomes Y, 7, 14, 15, 16, and 19. This study suggests that gain of 1q as the sole cytogenetic abnormality may be sufficiently mutagenic to favor leukemogenesis and hematopoietic tissue degeneration (trilineage myelodysplasia).

Transformation of primary myelofibrosis with 20q- in Philadelphia-positive acute lymphoblastic leukemia: case report and review of literature.

A 56-year-old male with chronic idiopathic myelofibrosis and cytogenetic finding of 20q- after a period of 10 months developed acute Philadelphia-positive lymphoblastic leukemia. Immunophenotyping of peripheral blood by flow cytometry showed HLA-DR, CD34, CD19, CD22, CD10, CD33, and CD11b positivity. Cytogenetic analysis revealed the presence of 20q- and Philadelphia chromosome t(9;22)(q34:q11) at the time of disease transformation to ALL. The JAK2V617F mutation was not found. This is a very rare case of simultaneous presence of two cytogenetics abnormalities and evolution of primary idiopathic myelofibrosis to Philadelphia-positive acute lymphoblastic leukemia.

Mixed phenotype acute leukemia of T/myeloid type with a prominent cellular heterogeneity and unique karyotypic aberration 45,XY, dic(11;17)

Introduction.u2002 A 26‐yr‐old male patient with mixed phenotype acute leukemia of T/myeloid type with prominent leukemic cell heterogeneity, and the presence of a so far unreported karyotype aberration in this type of acute leukemia 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) is presented.

Therapy-related acute leukemia in two patients with multiple sclerosis treated with Mitoxantrone

Two cases of therapy-related acute leukemia (TRAL) after the use of Mitoxantrone for the treatment of secondary progressive multiple sclerosis (MS) are reported. They were extracted from the group of 42 consecutive patients with TRAL diagnosed and treated in single centre between 2000-2010. They were the only two with MS and the only two treated with Mitoxantrone. The first patient was a 43-year-old male with a previous history of MS of 15-year-duration, who developed acute promyelocytic leukemia 9 months following Mitoxantrone therapy (cumulative dose 120 mg). The second patient was a 55-year-old female suffering from MS for 16 years, who developed acute mixed-phenotype leukemia, T/myeloid type, with 46,XX,del(7)(p13)[12]/47,XX,idem,+3/[6]/46,XX[2], 15 months after completion of Mitoxantrone therapy (cumulative dose 100mg). Acute mixed-phenotype leukemia, T/myeloid type is for the first time described in the context of prior Mitoxantrone therapy. Although the incidence of TRAL in relation to Mitoxantrone pretreatment is rare, we should be vigilant for the prompt identification of this adverse event.

Novel chromosomal translocation (17;22)(q12;q12) in a case of myelodisplastic syndrome characterized with signs of hemolytic anemia at presentation.

Myelodysplastic syndromes (MDS) are clonal stem cell diseases that can result in cytopenias, dysplasia in one or more cell lineages, infective hematopoiesis, and increase the risk of progression to acute myeloid leukemia (AML). MDSs are characterized by several recurrent cytogenetic defects, which can affect diagnosis, prognosis, and treatment. Some of that chromosomal alterations are associated with very poor prognosis. Conventional cytogenetics cannot accurately define the rearranged karyotype. Instead, molecular cytogenetics analyses can provide important diagnostic and prognostic information for patients affected by MDS, allowing the characterization of the whole mutational spectrum and, mainly, novel chromosomal lesions. In this paper, we report a MDS case with a novel chromosomal translocation [t(17;22)(q12;q22)], described for the first time here. Following Giemsa-banding karyotyping, fluorescent in situ hybridization analyses, by using chromosome-specific probes, displayed the breakpoint regions at chromosomes 17 and 22, within which intra and inter-chromosomal segmental duplications (SD) are present. Because of the occurrence of SDs in breakpoint region, it was not possible to finely define the genomic regions where breaks fell. Further investigations could be required to better understand the molecular basis of the novel translocation t(17;22)(q12;q12) acting in MDS context and to explain if SDs could contribute to the pathogenesis of MDS.

Single institute study of FLT3 mutation in acute myeloid leukemia with near tetraploidy in Serbia

Patients with de novo acute myeloid leukemia (AML) and near-tetraploid or completely tetraploid karyotype at presentation are rare. We present four patients with near-tetraploidy/tetraploidy in a cohort of 426 consecutive AML patients (0.98%) in respect to their cytogenetic findings, immunophenotype pattern, response to chemotherapy, course of disease and molecular analyses including tyrosine kinase receptor FLT3 gene, NRAS gene, and tumour suppressor gene, p53. We have found FLT3/ITD mutation only in one patient among the four with near-tetraploidy. The main finding is that these patients had a variable clinical course, with two having a long period of remission (36 and 12 months) and two died, not having achieved remission.

Acute Myeloid Leukemia Associated With Near-Tetraploid Karyotype and Mutations in the FLT3 Gene

Tetraploidy and near-tetraploidy are rare in acute myeloid leukemia (AML), contrary to other hematological disease. In this paper we describe a case of a 52-year-old male with AML associated with tetraploidy, mutation in tyrosine kinase receptor FLT3 , and very short survival. At presentation maculopapular rash with crustae, lymphadenopathy, and hepatosplenomegaly was diagnosed. The blasts comprised 80% of marrow nucleated cells (POX negative and PAS finely granular positive). Immunophenotyping done on marrow cells was (CD34, HLA DR, CD14, CD64, CD33, CD11b, and CD15) and correlated with the acute monoblastic leukemia. Detection of FLT3 mutation was done by polymerase chain reaction (PCR). Cytogenetic analysis show: 85–93, XXYY,inc(cp5)/46,XY. Based on these considerations, we suggest the detection of FLT3 mutations as a diagnostic procedure for all AML patients.nn* AMLn : acute myeloid leukemian PCRn : polymerase chain reactionn ALLn : acute lymphoblastic leukemian FLT3n : fms-like tyrosine kinase 3n APLn : acute promyelocytic leukemia