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We present an unusual case study on acute myeloid leukemia associated with t(1;3) and extreme thrombocytosis, along with a thorough review on relevant literature of t(1;3) cases (58 patients). On the basis of this study and literature review, thrombocytosis (>400,000/μL) is a relatively common finding in one third of patients with t(1;3), whereas increase of platelet count by more than 1,000,000/μL is an extremely rare phenomenon, even among patients with t(1;3). To our knowledge, this study is the only documented case that recorded more than 2,000,000/μL of extreme thrombocytosis in a de novo acute myeloid leukemia patient with t(1;3) at initial diagnosis. Because only a few patients with t(1;3) responded to conventional chemotherapy, more aggressive therapy such as stem-cell transplantation should be considered to improve patient survival in t(1;3) cases., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Polycythemia vera (PV) and essential thrombocytosis (ET) are clonal chronic myeloproliferative disorders originating from a multipotent stem cell. Bone marrow examinations reveal chromosomal abnormalities in 15-43% of PV patients and 5% of ET patients, but no specific recurring abnormality has been found to date. We aimed to find cytogenetic aberrations in PV and ET by comparative genomic hybridization (CGH), a relatively new molecular cytogenetic technique. In this study, CGH analysis was performed on peripheral blood leukocytes of 12 PV patients and 8 ET patients. One patient (8.3%) with PV had an abnormal karyotype with a deletion in 7q11.2 and one patient with ET (12.5%) had a gain in 18p. Peripheral blood analysis by CGH revealed a low frequency of cytogenetic abnormalities in PV and ET patients. However, using CGH we were able to detect two cytogenetic aberrations that were not reported previously in these disorders.

A 66-year-old man was diagnosed 10 years ago with thrombocytosis and treated with hydroxyurea. Recently, his condition deteriorated and he was found to have 68% blasts in the blood and AML-M5a. Conventional cytogenetic analysis and fluorescence in situ hybridization studies using 11-painting and MLL probes showed that chromosome 11 had duplications or triplications; the markers were also derived from the chromosome 11-MLL region. Therefore, we have demonstrated segmental rearrangement of chromosome 11 involving the MLL region resulting in multiple copies of the MLL gene.

We report a novel chromosomal translocation (X;5)(q13;q33) in a woman with no history of prior chemotherapy or radiotherapy, found to have essential thrombocythemia. Aberrations in chromosome 5, mostly deletions of 5q, have been described in essential thrombocythemia; however, a t(X;5) translocation has not been reported.

Essential thrombocytosis (ET) is a clonal, chronic myeloproliferative disorder (MPD) originating from a multipotent stem cell. To date no specific cytogenetic marker has been found in ET. It was recently reported that chromosomal aberrations have been detected by fluorescence in situ hybridization (FISH) in patients with normal karyotypes or nonanalyzable metaphases. Therefore, we evaluated whether trisomies 8 and 9, which are commonly found in MPDs, can be detected in ET by FISH and compared the results with chromosome analysis. Peripheral blood mononuclear cells of patients with essential thrombocytosis were studied by classical chromosome banding and by FISH. We used biotin labeled alpha satellite of chromosome 8 and biotin labeled beta satellite of chromosome 9 as probes for the FISH studies. FISH detected 5 patients with trisomy 8 and 5 with trisomy 9 of the 18 patients evaluated. No trisomy was found by cytogenetic studies. The trisomies were detected by FISH in only a minority of the cells. No correlation was found between the presence of a trisomy and clinical characteristics. FISH is a sensitive method for the detection of trisomies 8 and 9 in patients with ET. The common finding of these chromosomal aberrations in MPD suggests that genes associated with myeloid proliferation are located on these chromosomes. Standardization of interphase cytogenetics is needed before this technique can be accepted for routine use in the clinic.

A case of essential thrombocythemia (ET) with extreme thrombocytosis in a 70-year-old male patient is described. The cytogenetic analysis revealed a pathologic clone with the following previously unreported, unusual karyotype: 46,XY,t(13;14)(q32:q32.3) and pericentric inversion of chromosome 9. The possible association of t(13;14) with the high platelet count is discussed.

Essential thrombocythemia (ET) was diagnosed clinically in three patients Karyotypic analysis and reverse transcription polymerase chain reaction for the bcr-abl chimeric transcript showed that two were Philadelphia chromosome (Ph) positive, bcr-abl positive, whereas the third was Ph negative, bcr-abl positive. The first patient received an allogeneic bone marrow transplantation but relapsed as localized blastic transformation, thus behaving similarly to chronic myeloid leukemia (CML). However, the other patients showed clinical courses more in keeping with ET. Essential thrombocythemia with BCR rearrangements may resemble CML but there are clinical differences. These may be due to genetic changes in addition to the BCR rearrangement.

Defects of 3q in bands q21 and q26 have been reported in more than 70 cases of acute nonlymphocytic leukemia (ANLL), myelodysplastic syndrome (MDS), and myeloproliferative disorder (MPD) in blast crisis. In this paper three additional patients are described: patient 1 with refractory anemia with excess of blasts in transformation (RAEB-T) and inv(3)(q21q26), patient 2 with RAEB-T and t(3;3)(q21;q26), and patient 3 with myelofibrosis with myeloid metaplasia (MMM) in blast crisis and inv(3)(q21q26). In addition to 3q rearrangements, monosomy 7 and del(7)(q22q36) were observed in patients 1 and 2, respectively. In the three patients, the most characteristic clinical features were elevated platelet counts, marked hyperplasia with dysplasia of the megakaryocytes, and poor prognosis. Although disturbance of thrombopoiesis was not systematically observed in all patients with t(3;3)(q21;q26), inv(3)(q21q26), and ins or dup(3)(q21----q26), study of the 77 cases reported and of the three cases presented here brings further evidence to the existence of a cytogenetic syndrome involving bands q21 and q26 simultaneously, which represents a subtype of ANLL, MDS, and MPD, characterized by normal or elevated platelet counts, hyperplasia with dysplasia of megakaryocytes, multilineage involvement, young median age of patients with MDS, preferential involvement of women in t(3;3), high incidence of chromosome 7 defects in MDS and ANLL, short duration of the MDS phase, no response to chemotherapy, short survival, and por prognosis.

We report two patients with a myelodysplastic syndrome and the Philadelphia (Ph) chromosome. The first patient was a 73-year-old man who was diagnosed as having a chronic myelomonocytic leukemia in combination with features suggestive of a myeloproliferative syndrome. Chromosomal analysis showed a normal karyotype in the majority of cells, mixed with metaphases containing a standard Ph translocation, t(9;22)(q34;q11), as well as a translocation between chromosome 4 and 6: t(4;6)(p15;p12). Southern blot analysis showed breakpoint cluster region rearrangement as observed in classic chronic myeloid leukemia. The second patient was a 63-year-old man with a myelodysplastic syndrome, type refractory anemia. Cytogenetic study of bone marrow cells at the time of diagnosis revealed a normal karyotype: 46,XY. The initial myelodysplastic syndrome evolved to a myeloproliferative phase with progressive leukocytosis and thrombocytosis. During the terminal phase the Ph chromosome was discovered in 100% of the examined cells. We discuss the correlation between MDS and myeloproliferative diseases, the de novo acquisition of the Ph chromosome during the course of a myelodysplastic syndrome, and review the literature.

We identified three patients with an acquired Robertsonian translocation among 1,200 patients with hematopoietic malignancy. In each case the translocation served to produce partial chromosomal trisomy or tetrasomy within the malignant clone. Acquired Robertsonian translocation represents another, although rare, mechanism of clonal evolution in malignant cells.

A patient with refractory anemia with excess blasts, ringed sideroblasts, and thrombocytosis was found on cytogenetic analysis to have trisomy 19 as the sole abnormality. Although trisomy 19 in combination with other chromosomal anomalies has been encountered in association with a variety of hematologic malignancies, many solid tumors, and the myelodysplastic syndrome, its occurrence as the only cytogenetic aberration is rare and has not been reported in association with thrombocythemia.

A patient with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia is described who also developed an abnormality of chromosome #3, i.e., t(3;20)(p21;p13), in blast crisis. This abnormality may be connected with the advent thrombocythemia. The disease was a thrombopenia in the initial phase.

The clinical and cytogenetic findings of a patient with the preleukemic syndrome and a structural rearrangement involving both chromosomes No. 3 are described. The karyotypic abnormality consisted of an insertion of a part of the long arm of one chromosome No. 3 into the other, i.e., ins(3;3)(q27;q21q27). A prominent feature of the bone marrow was a marked megakaryocytic hyperplasia. The platelet count temporarily exceeded 1000 x 10(9)/liter. The findings of the present case, together with similar observations by others, suggest that the long arm of chromosome No. 3 may contain a region involved in the regulation of megakaryopoiesis.

Ten patients with a hematologic disorder and a clone of cells with trisomy 9 in the bone marrow were studied in order to investigate the clinical significance of this chromosome anomaly. In five of the patients, trisomy 9 was the only anomaly; in four, there was also trisomy 8; and in one, a Y chromosome was also lacking. Four patients had a myelodysplastic syndrome, and six had a myeloproliferative disorder. Interestingly, four patients had primary thrombocytosis.

A woman with thrombocytopenia that progressed to aplastic anemia, and her brother, who had persistent thrombocytopenia, both had a constitutional t(13;14) translocation. Six other family members, in three generations, had the same translocation, but no hematologic disorder. There was evidence suggestive of increased chromosomal fragility in lymphocyte cultures from two members of the kindred, but not in the two patients. The findings support a postulated association between the t(13;14) and hematologic disorders, but whether the mechanism involves an inherited defect in chromosomal stability is unproved.

In 33 patients with essential thrombocythemia, a specific chromosomal abnormality ( 21q -) could not be confirmed. All patients in this series met rigid criteria for diagnosis of this myeloproliferative disorder.