Elsevier

Leukemia Research

Volume 53, February 2017, Pages 20-27
Leukemia Research

Tetraploidy/near-tetraploidy acute myeloid leukemia

https://doi.org/10.1016/j.leukres.2016.11.016Get rights and content

Highlights

  • T/NT AML often shows distinctive morphology.

  • T/NT AML often co-exist with other poor prognostic factors and generally has a poor outcome.

  • Non-complex T/NT conveys an intermediate risk, and shows a better prognosis than complex T/NT.

Abstract

A tetraploid/near tetraploid (T/NT) karyotype is a rare finding in acute myeloid leukemia (AML). Here we report 38 AML patients with a T/NT karyotype, including 26 men and 12 women with a median age of 65 years. T/NT karyotype was detected at initial diagnosis of AML in 16 patients, and acquired during the course of disease in 22 patients. All patients showed large blasts with frequent prominent nucleoli, cytoplasmic vacuoles and/or inclusions, nuclear irregularity and/or budding. Eleven patients had a non-complex and 27 had a complex T/NT karyotype; 21 patients also had pseudodiploid and/or triploid clones. After T/NT karyotype detection, 32 patients received chemotherapy and 10 also received stem cell transplant. After a median of 6.2 months follow-up, 32 patients died of disease or complications, 5 were alive with complete remission, and 1 alive with persistent AML. Median overall survival (OS) was 5 months. Patients with a non-complex T/NT karyotype had a significantly superior OS compared to those with a complex T/NT karyotype (10.7 vs. 3.4 months, p = 0.0280). We conclude that T/NT karyotype in AML is often associated with distinctive morphologic features and conveys generally poor outcomes. Distinction of complex versus non-complex T/NT karyotype provides further prognostic information.

Introduction

Tetraploidy (4n, 92 chromosomes) without other numerical or structural abnormalities is occasionally observed at a low level in normal bone marrow (BM), likely representing mitotic megakaryocytes [1] or cells at anaphase stage in which paired sister chromatids are separated. Tetraploidy or near tetraploidy (T/NT) (81–103 chromosomes) karyotype with numerical and structural abnormalities is often associated with tumorigenesis and has been reported in acute myeloid leukemia (AML) [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], acute lymphoblastic leukemia (1–2%) [12], T- or B-cell lymphomas [13], [14], and solid tumors [15].

T/NT karyotype is rare in AML and only single cases or small case series have been reported to date. In these case reports, T/NT AML has been described to occur preferentially in elderly male patients and is morphologically featured by large blasts. However, due to its rarity, the clinical significance and prognostic value of T/NT karyotype in AML is not well defined. In many studies, a T/NT karyotype was categorized as a complex karyotype which belongs to high-risk cytogenetic group, however, some reports have described patients with T/NT AML experiencing a similar outcomes as patients with intermediate-risk group [2], [4].

To better characterize the clinical behavior and pathological features of T/NT AML, we searched the database for all AML patients with a T/NT karyotype at our institution in the past 15 years and identified 38 patients. We present the clinicopathologic and cytogenetic findings in these patients and correlate with patients’ outcomes.

Section snippets

Patients

We searched the database of the Clinical Cytogenetics Laboratory at The University of Texas MD Anderson Cancer Center (MDACC), for all cases with T/NT karyotype between the years of 2000–2015. We then focused on patients with a diagnosis of AML. Tetraploid metaphase (96 chromosomes) without any structural or numerical abnormalities involving 1–2 metaphases could be occasionally (0.5% of cases based on our lab records) observed in AML bone marrow culture. These tetraploid metaphases are usually

Patients

A total of 38 patients with AML and T/NT karyotype were identified during a 15-year period, comprising ∼0.7% of all AML patients during this interval at our institution. These patients included 26 (68%) men and 12 (32%) women with a median age of 65 years (range, 21–88) (Table 1). Nine (24%) patients had a proceeding clinical history of myelodysplastic syndromes (MDS) with transformation to AML after a median interval of 6 months (range, 1–101 months), T/NT karyotype was detected at the time or

Discussion

T/NT karyotype is a rare cytogenetic finding in AML, occurring in 0.7–1.2% of adult AML patients based on our data and other studies [7], [8]. Patients with T/NT AML are typically of advanced age with male predominance, and the blasts have distinctive morphologic features. However, the prognosis of this group of patients is contextual, depending on other factors.

Cytogenetic abnormalities play an important prognostic role in AML patients and have been stratified into different risk groups. In

Disclosures/conflict of interest

The authors report no potential conflicts of interest.

Acknowledgements

The authors would like to thank colleagues from department of hematopathology and clinical cytogenetic laboratory for their great inputs.

References (32)

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