Unbalanced jumping translocation involving 3q in myeloproliferative disease.

An 87-year-old woman was diagnosed with unclassified myeloproliferative disease having an acquired jumping translocation with the long arm of chromosome 3 translocating to the short arm telomeric region of chromosome 8 (major clone) and the long arm telomeric region of chromosome 10 (minor clone). Each abnormal clone was also associated with an extra copy of chromosome 8. Although there was no evidence of transformation to an acute leukemia, the patient deteriorated until her demise 7 months after disease presentation. There have been fewer than 70 cases of acquired jumping translocations reported in the literature. To our knowledge, this is the first acquired jumping translocation case to be reported in a patient with myeloproliferative disease.

Transformation of cytogenetically normal chronic myelomonocytic leukaemia to an acute myeloid leukaemia and the emergence of a novel +13, +15 double trisomy resulting in an adverse outcome.

A 58-year-old man was admitted with symptoms of lethargy and easy bruising for four months duration. Peripheral blood (PB) analysis revealed a white blood cell count (WBC) of 15.9 x 10(9)/l with monocytes 5.4 x 10(9)/l. Bone marrow (BM) was hypercellular with 15% blasts, monocytosis and trilineage dysplasia. Conventional cytogenetic analysis (G-banding) detected an apparently normal male karyotype (46,XY). A diagnosis of chronic myelomonocytic leukaemia (CMML) was made. After 3 years, PB analysis revealed a WBC count of 22 x 10(9)/l and a predominance of blasts. BM aspirate analysis also revealed 89% myeloid blasts and G-banding detected the emergence of an abnormal clone harbouring an extra copy of chromosomes 13 and 15. A diagnosis of disease transformation to acute myeloid leukaemia (AML) was made. Post chemotherapy BM aspirate was very hypocellular and the abnormal +13, +15 clone was still present suggesting primary refractory disease. A second course of chemotherapy was only administered for 24 hours due to complications. The abnormal +13, +15 clone was still present and it was decided that no further treatment apart from palliative care could be offered. The patient died 11 weeks later, five months after AML transformation. This is the first description of a cytogenetically normal CMML patient transforming to AML with the emergence of a unique +13, +15 double trisomy resulting in an adverse outcome.

Tetrasomy 13 as the sole cytogenetic abnormality in acute myeloid leukemia M1 without maturation.

We report a case of acute myeloid leukemia (AML) M1 showing a 48,XY,+13,+13 karyotype. Treatment was according to the Medical Research Council AML14 trial protocol with two courses of DAT chemotherapy. Postchemotherapy bone marrow examination failed to show complete remission or cytogenetic normalization. Despite having resistant disease, the patient initially remained clinically well although requiring regular blood transfusions for anemia. However his leukocyte count gradually increased and he became symptomatic. He was treated subsequently with FLAG but died approximately 2 weeks later, 6 months after first presenting. Tetrasomy 13 as the sole cytogenetic abnormality has not been reported previously in M1 AML and has only been reported in three other AML cases, all with an immature phenotype and poor outcome.

Jumping translocation in acute monocytic leukemia (M5b) with alternative breakpoint sites in the long arm of donor chromosome 3.

An 86-year-old man presented with acute hepatic failure, worsening thrombocytopenia, and anemia having been diagnosed and managed expectantly with cytogenetically normal RAEB-1. After 20 months a diagnosis of disease transformation to acute monocytic leukemia (M5b) was made. Conventional G-banded analysis of unstimulated bone marrow cultures demonstrated a jumping translocation (JT) involving proximal and distal breakpoints on donor chromosome 3 at bands 3q1?2 and 3q21, respectively. Recipient chromosomes included the long-arm telomeric regions of chromosomes 5, 10, 14, 16, and 19. A low-level trisomy 8 clone was also found in association with both proximal and distal JT clones. Conventional G-banded analysis of unstimulated peripheral blood cultures detected the proximal 3q1?2 JT clone involving recipient chromosome 10 several weeks after transformation to acute monocytic leukemia. Interestingly, JTs involving recipient chromosomes 5, 14, 16, and 19 were not detected in this peripheral blood sample. Palliative care was administered until his demise 2.2 months after disease transformation. There have been fewer than 70 cases of acquired JTs reported in the literature, including one myeloproliferative neoplasm and five acute myeloid leukemias involving a single breakpoint site on donor chromosome 3. Our case is unique as it is the first acquired case to demonstrate a JT involving alternative pericentromeric breakpoint sites on a single donor chromosome consisting of a proximal breakpoint at 3q1?2 and a more distal breakpoint at 3q21.