Jumping translocations of 1q refer to the break-off of chromosome 1q as a donor fusing to two or more recipient chromosomes. We detected jumping translocations of 1q in three patients with initial diagnosis of myelodysplastic syndrome (MDS) and later progression to acute myeloid leukemia (AML). Review of literature found jumping translocations of 1q in 30 reported cases of MDS and AML. The cytogenetic findings from these 33 cases showed that seven cases had a stemline clone and 26 cases had de novo jumping translocations of 1q in which 5% of cell lineages had additional structural rearrangements. In 75% of cases, the 1q donor jumped to the short arm of recipient acrocentric chromosomes. Approximately 82% of the fusions occurred in the telomeric regions of short and long arms and 18% occurred in the pericentric or interstitial regions of recipient chromosomes. Hypomethylation of the donor 1q pericentromeric region and shortened telomeres in recipient chromosomes were associated with the formation of jumping translocations. Jumping translocations of 1q as an indication of chromosomal instability pose high risk for progression of MDS to AML and a poor prognosis. Further understanding of underlying genomic defects and their clinical significance will improve overall treatment and patient care.
Jumping translocations are a rare type of cytogenetic abnormality initially detected in a case of acute monocytic leukemia and later found in various types of leukemias [
A retrospective review of cases with MDS and AML from the CytoAccess database in Yale Cytogenetics Laboratory found three cases with jumping translocations of 1q [
This male patient was first evaluated at age 59 with an indication of leukopenia and mild anemia; cytogenetic analysis found a normal result. Two years later, this patient was diagnosed with MDS and chromosomal analysis on a bone marrow aspirate showed an abnormal clone with jumping translocations of 1q. The karyotype was as follows: 46,XY,der(15)t(1;15)(q12;p12)
This patient, a 63-year old male, was referred with MDS by an indication of MDS with excess blasts. Chromosomal analysis showed a karyotype of 46,XY,der(15)t(1;15)(q12;p11.2)
This patient was a male at age 73 when diagnosed with MDS. Chromosomal analysis showed a karyotype of 46,XY,der(15)t(1;15)(q12;p11.2)
The cytogenetic findings of successive studies from these three patients all showed persistent jumping translocations of 1q with an increased percentage in bone marrow cells. The chromosome patterns of jumping translocations of 1q are shown in Figure
(a) Jumping translocations of 1q observed in the three patients. The jumping translocation in each cell lineage is shown inside a circle. Arrow points to an additional rearrangement evolved in a cell lineage. (b) Epigenetic alterations in the formation of jumping translocations of 1q. Hypomethylation of 1q12 pericentric heterochromatin induced chromatin decondensation, triradial formation, and break-off of 1q donor segment. Loss of telomeric function by variant telomeric repeats and shortened telomeres produced instable recipient chromosomes. The successive fusions between break-off donor segment and recipient chromosomes resulted in clonal abnormalities with cell linages sharing gains of donor chromosome segment.
Patterns of donor and recipient chromosomes in jumping translocations of 1q of MDS and AML patients.
The results from these 33 cases revealed the chromosomal fusion patterns between the 1q donor chromosome and different recipient chromosomes. However, all studies done by routine chromosome analysis lacked the molecular characterization of breakpoints involving the chromosome fusion, underlying genomic imbalances, and tumor gene mutations. A recent study using genomic array testing and targeted gene panel next-generation sequencing detected the 100–107 Mb duplication of 1q with breakpoints in 1q21.1-q21.3 region and recurrent mutations in the TET2 and SF3B1 genes [
Approximately one-third of MDS/AML cases with jumping translocations of 1q either emerged from a stemline abnormal clone or evolved additional clonal abnormalities and two-thirds were detected as de novo chromosomal abnormalities. Shortened telomeres and many variant telomeric repeats were detected in the fusion points from jumping translocations of 1q in a case of MDS progressed to AML; this result suggested that the extended proliferation of cancer cells might be related to the loss of telomeric function [
The progression of MDS to AML and poor prognosis were noted in the present three cases with jumping translocations of 1q. This result was consistent with previous findings in which jumping translocations of 1q were associated with a high risk of progression to AML and poor prognosis and thus warranted aggressive therapy [
In summary, jumping translocations of 1q have been shown as an indication of chromosomal instability likely induced by epigenetic alterations of hypomethylation and shortened telomeres. The jumping translocations of 1q showed unique rearrangement patterns with multiple cell lineages which all have a gain of donor chromosome segment and lack other complex structural or numerical rearrangements. It is not clear whether these epigenetic alterations occur independently as a two-step event or concurrently by driving genetic defects. Further molecular analyses to understand the genetic defects causing jumping translocations of 1q and related disease-causing mechanism can facilitate targeted therapy for this type of MDS and AML.
The authors declare that they have no conflicts of interest.