Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study

Abstract

Cytogenetic and clinical details are presented for 66 patients with myeloid malignancy and chromosome abnormalities of 3q21 and/or 3q26 (3qabns). Bone marrow and/or peripheral blood morphology was assessed for 52 cases. 3qabns in Philadelphia negative (Ph-ve) and positive (Ph+ve) cases were inv(3)(q21q26), (21 Ph-ve, 6 Ph+ve); t(3;3)(q21;q26) (nine Ph-ve, four Ph+ve); and t(3;21)(q26;q22) (four Ph-ve, six Ph+ve). Ph-ve cases also had t(1;3)(p36;q21) (three cases), and t(3;5)(q21;q31)/(q21;q35)/(q26;q21) (five cases aged < 40 years). Three cases, aged < 30 years, had t(3;12)(q26;p13) which defines a new 3qabn subgroup. Monosomy 7 and/or 5q- accompanied inv(3) or t(3;3) in 17/30 cases. All cases had a myeloid malignancy (predominantly AML M1, M4 or M7), frequent trilineage myelodysplasia, and markedly abnormal megakaryopoiesis with micromegakaryocytes (< 30 microns). Thrombocytosis occurred in two cases only. Most Ph+ve cases were in myeloid blast crisis and in Ph+ve cases alone, micro-megakaryocytes were uniquely small (10 microns) in 7/11 cases. There were equal numbers of males and females. Seven secondary leukaemias were found in Ph-ve cases with inv(3), t(3;3), t(3;21), t(1;3) or del(3)(q21). Three cases with t(3;21) (one Ph+ve) were de novo AML or had de novo aplastic anaemia. Survival was rarely greater than 12 months from detection of the 3qabn.

Translocation (2;3)(p21;q26) as the Sole Anomaly in a Case of Primary Myelofibrosis

“…The same conclusion can be drawn from CML patients where the detection of the t(2p;3q) coincided with rapid conversion to blast crisis [8,9]. Our observation also confirms previously established correlations between rapid blastic transformation and 3q abnormalities [13,14]. Other common features of 3q26 aberrations are also encountered, such as an abnormal platelet count and micromegakaryocytes [14].…”

Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells

“…The 3q21q26 syndrome is associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), and is characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and poor prognosis (Secker-Walker et al, 1995). A similar type of MDS/AML has been reported in the recurrent t(1;3)(p36;q21).…”

Forced expression of the leukemia-associated gene EVI1 in ES cells: a model for myeloid leukemia with 3q26 rearrangements

“…[1][2][3] A chromosomal site that frequently is rearranged in many chromosomal translocations and inversions identified in myeloid leukemia is the chromosomal band 3q26. 2,[4][5][6][7][8][9][10] The EVI1 gene is located at 3q26 and targeted by the rearrangements and was first identified in the mouse as the site of retroviral integration associated with myeloid leukemia, and later cloned from human cancer cells. 11,12 In general, defects of bands 3q26 and 3q21 occur simultaneously by inversion or homologous translocations of chromosome 3, and have been reported in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).…”