Most frequently observed in chronic myeloproliferative disorders, occurs with higher frequency in patients with chronic idiopathic myelofibrosis, polycythemia vera and post-polycythemic myelofibrosis; may be present either at diagnosis or during transformation to advanced stages of the disease.

Described in 20 cases (11 males, 9 females): 1 biphenotypic leukemia (16 years old male); 1 B-cell lymphoma (73 years old female); 2 acute myeloid leukemia (AML) patients (1 male 71 years old, 1 female 28 years old); and in 16 patients with myelofibrosis with myeloid metaplasia (9 males; 7 females): eleven patients had myelofibrosis with myeloid metaplasia, three post-polycythemic myeloid metaplasia, and one post-thrombocythemic myeloid metaplasia; one of these patients, a 47 years old male, progressed to AML. From the known data of 14 patients with myelofibrosis, median age was 65.5 years (range, 38-72 years).

In the largest study, the anomaly was associated with splenomegaly, elevated WBC count, elevated levels of alkaline phosphatase and lactate dehydrogenase; median overall survival was 7.8 years: five patients have died (one transformed to acute myeloid leukemia and the others died because of sepsis or thrombosis).

Breakpoints may be controversial and difficult to ascertain in poor quality preparations. Recently, the same breakpoint on 6p21.3 and clustering of breakpoints near the paracentric region 1q21-23 was described in 14 patients with myelofibrosis with myelocytic metaplasia.

Sole anomaly in 9 cases (2 AML and 7 cases with myelofibrosis); no recurrent additional anomaly observed in patients with complex karyotypes. 4 patients had two or more different clones (1 patient with biphenotypic leukemia and 3 myelofibrosis cases); among them 2 patients had 1q21-23 rearrangements involving the homologous chromosome 1.

The presence of the der(6)t(1;6) results in partial trisomy for 1q21-23 to 1qter and in loss of 6p21 to 6pter. The pathogenetic significance may be the consequence of gain of gene(s) on 1q and/or haplo-insufficiency of gene(s) from 6p and alternatively, rearrangements of one or more genes at the breakpoints. The significance of the 6p21 breakpoint is unclear; however a number of published reports of myelofibrosis with chromosome 6p breakpoints in the region raise the possibility of a gene involved in the pathogenesis of this hematologic disorder. The inability to identify common breakpoints on 1q, suggests that an increase in gene copy number is a pathogenetic event. Whether trisomy 1q is a secondary event to a primary (cryptic? e.g. JAK2 V617F mutation) anomaly as well as the roles of methylation, cytotoxic treatments and the underlying molecular consequences of the rearrangement remain to be determined.