Myeloproliferative disorders, multiple myeloma and lymphoid malignancies

Reported in diverse hematologic disorders

Different factors like constitutional fragility of the 1q heterochromatin, cytotoxic drugs, ionizing radiation and/or oncogenic viruses are suspected to be implicated in the origin of 1q rearrangements.

Reported at least in 20 cases (Table 1); median age 52 years (range 20-86), balanced sex ratio (11M/9F). Found in: chronic myeloproliferative disorders (8 of the 20 available cases): polycythemic myelofibrosis (PPMF) in 1 case, essential trombocytopenia (ET) in 1 case, chronic myeloid leukemia (CML) in 1 case; myelodysplastic syndromes (MDS) in transformation in 3 patients as well as in acute myeloid leukaemia (2 patients), multiple myeloma (4 patients) and in lymphoid malignancies (8 patients).

Whether karyotypic changes associated with extra copies of 1q are primary events or they are induced during disease evolution as a side effect of cytotoxic treatments is unclear. May be found as a sole anomaly in chronic myeloproliferative disorders (Andrieux et al, 2003; Tanaka et al, 2006), indicating that der(1;13) might be a primary change in myeloid disorders. Occurred as part of complex karyotypes in multiple myeloma and lymphoproliferative malignancies, suggesting that 1q abnormalities may be secondary events in these diseases representing clonal evolution associated with natural disease evolution.

It is likely that the prognosis depends on the patient diagnosis in myeloid malignancies (chronic disease versus acute leukemia). Prognosis in multiple myeloma and lymphoid malignancies is uncertain.

Acquired whole-arm chromosome translocations with involvement of the 1q heterochromatin are accompanied by genomic imbalances in hematologic malignancies. The chromosome 1 pericentromeric heterochromatin is a notoriously an unstable chromosomal region that is involved in diverse chromosomal rearrangements leading to gene dosage abnormalities. The acquisition of the long arm of chromosome 1 results in trisomy of the whole-arm of chromosome 1 and partial monosomy of the involved chromosome. Duplication of the chromosome segment of 1q11-1q32 is commonly observed in these rearrangements, indicating that certain chromosome 1 regions, especially 1q21-1q32 might harbor pathogenetically relevant oncogenes. The unbalanced nature of the der(1;13)(q10;q10) indicates that the gain of 1q may play an important role in neoplastic transformation and/or disease progression. Although a der(1;13)(q10;q10) translocation has been reported in various neoplastic conditions, such as multiple myeloma and lymphoma, this translocation is also observed in both chronic and acute myeloid disorders. The observation of this anomaly was closely associated with leukemic transformation in myeloid malignancies suggesting that der(1;13)(q10;q10) might be a rare but nonrandom primary change in these disorders preceding or accompanying disease evolution.