Transformation of myelodysplastic syndrome with isolated 5q-syndrome to chronic myelogenous leukemia with a novel complex BCR/ABL1 translocation with rapid progression to blast crisis

Abstract

We report a case of a 72 year old female who was referred to our institution in August 2010 for Myelodysplastic syndrome (MDS) with a deletion of part of the long arm of chromosome 5 [i.e., del(5) (q12q33)]. In June 2014, she transformed to Chronic Myelogenous Leukemia (CML), where cytogenetic and FISH analysis of the bone marrow (BM) revealed the del(5q) in 1.5% of nuclei and a complex BCR/ABL1 translocation [i.e., 45,XX,t(9;15;22)(q34;p10;q11.2),-22]. Six weeks later, in July 2014, she transformed to an Acute Myelogenous Leukemia (AML) blast crisis. RT-PCR was positive for BCR/ABL1 transcript. The patient was treated with a tyrosine kinase inhibitor, Nilotinib, then had a haploidentical allogeneic bone marrow transplant from her son, and was in remission after treatment. However, throughout the course of nine subsequent cytogenetic analyses, the patient continued to undergo clonal chromosome evolution, even during remission. Transformation from MDS del(5q) to CML with rapid progression to blast crisis has rarely been reported. To our knowledge, transformation with this complex translocation has never been described. Here we describe these rare cytogenetic findings and discuss possible mechanisms involved in the persistent and evolving clonal cytogenetic abnormalities seen during the clinical course of the disease.

Philadelphia chromosome positive chronic myeloid leukemia with 5q deletion at diagnosis

“…While chromosome 5q deletion has good prognostic implication in patients with de-novo myelodysplastic syndrome (MDS), when identified in patients with therapy related or de-novo acute myeloid leukemia, the prognosis is poor [ 27 , 28 ]. 5q deletion in CML has been reported only rarely in patients yet during therapy with conventional TKI or after stem cell transplantation [ 13 , 14 ]. Similarly, there have been cases that were initially diagnosed and managed as MDS associated with 5q deletion, who ultimately transformed to Ph + CML while retaining the original 5q deletion in the novel malignant clones [ 13 ].…”

“…5q deletion in CML has been reported only rarely in patients yet during therapy with conventional TKI or after stem cell transplantation [ 13 , 14 ]. Similarly, there have been cases that were initially diagnosed and managed as MDS associated with 5q deletion, who ultimately transformed to Ph + CML while retaining the original 5q deletion in the novel malignant clones [ 13 ]. Our patient, who presented with characteristic clinical and hematological features of CML in chronic phase, was initially a healthy individual, suggesting rather that the 5q- was acquired most likely after Ph chromosome appeared in the bone marrow cell clone.…”

“…clonal evolution may take place [ 10 , 11 ]. Such additional cytogenetic abnormalities may have significant effect on the disease profile and response to therapy [ 12 ].One of the rarely seen additional cytogenetic abnormalities is deletion in the long arm of a chromosome 5 (5q-); however, this has been reported yet only in CML-patients under during therapy [ 13 , 14 ].…”