DEK-CAN molecular monitoring of myeloid malignancies could aid therapeutic stratification

Abstract

The t(6;9)(p23;q34) is a recurrent chromosomal abnormality observed in 1% of acute myelogenous leukemia (AML), which generates a fusion transcript between DEK and CAN/NUP214 genes. We used a DEK-CAN real-time quantitative (RQ)-PCR strategy to analyze 79 retrospective and prospective samples from 12 patients. Five patients reached DEK-CAN negativity (sensitivity 10 À5 ); all underwent early allogeneic hematopoietic stem cell transplantation (median 5.5 months from diagnosis) with some demonstrating molecular positivity at the time of allograft. All four cases in CCR with adequate follow-up (median 18.5 months, range 13-95) demonstrate persistent molecular negativity, whereas all seven patients with persistent DEK-CAN positivity died at a median of 12 months from diagnosis (range 7-27). We conclude that DEK-CAN molecular monitoring by RQ-PCR in t(6;9) malignancies is a useful tool for individual patient management and that molecular negativity is indispensable for survival, but should not be a prerequisite for allografting in this rare, poor prognosis, subset of AML.

Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis

“…9,10 The current matchedpair analysis of the nationwide survey demonstrated that the OS and the non-relapse mortality, as well as the relapse rate, were independent of the presence of t(6;9)(p23;q34) in allogeneic HSCT recipients, thus suggesting that allogeneic HSCT may be able to overcome the unfavorable effect of t(6;9)(p23;q34) in AML patients.…”

“…[5][6][7][8] The translocation of chromosome (6;9)(p23;q34) forming the DEK/NUP214 fusion mRNA is observed in B1% of AML cases. 9 The characteristics of AML with t(6;9)(p23;q34) are known to include development at a younger age, 10 resistance to chemotherapy and a very poor prognosis. 9 Therefore, the presence of this karyotype in AML patients is an indication for HSCT; however, the impact of t(6;9)(p23;q34) on the outcome of HSCT remains unclear because of the rarity of this entity.…”

The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation

“…7 Although additional karyotypic aberrations are rare, they may appear during disease progression. 7,9 As a result of the translocation, the 3 0 part of the can gene from chromosome 9q34 is fused to the 5 0 end of the dek gene on chromosome 6p23, resulting in the formation of a chimeric dek/ can fusion gene on the 6p-derivative. The breakpoints on chromosomes 6 and 9 are located in one specific intron on each chromosome.…”

A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ‘poor prognosis’ myeloid malignancies

“…[1][2][3][4] Given the rarity of this particular subgroup of AML, previous reports attempting to describe the incidence, associated clinical features, and prognosis have been based on small patient cohorts, leaving some uncertainty about the nature of t(6;9) AML. [1][2][3][4] In order to better define this syndrome, a retrospective study of five Cooperative Groups databases (Southwest Oncology Group (SWOG), Cancer and Leukemia Group B (CALGB), Eastern Cooperative Oncology Group (ECOG), Childrens Oncology Group (COG) including the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)) was conducted.…”