The der(1;7)(q10;p10) defining a distinct profile from -7/del(7q) in myelodysplastic syndromes: A systematic review and meta-analysis

Abstract

Background and objective: Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by ineffective hematopoiesis due to stem cell abnormalities. Monosomy 7q aberrations are a common cytogenetic abnormality in MDS. Specifically, an unbalanced translocation der(1;7)(q10;p10) [der(1;7)] has been identified in MDS patients, which is a monosomy 7q aberration variant like -7/del(7q). However, knowledge of der(1;7)'s features remains limited. Existing studies have compared the clinical and genetic characteristics of der(1;7) to those of -7/del(7q) but yielded inconsistent findings. Accordingly, we conducted meta-analyses comparing der(1;7) to -7/del(7q).

Methods: Publications were searched from the following databases up to January 10, 2023: Pubmed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov. Eligible studies were assessed for risks of bias. Relevant data were extracted from included studies and analyzed using random-effects models. Publication bias was evaluated and sensitivity analyses were performed.

Results: The comparative meta-analyses included 405 MDS patients with der(1;7) from nine studies. The analysis revealed that der(1;7) was associated with a greater male preponderance (86.1% vs. 68.3%, Odds Ratios (ORs) 2.007, p < 0.01) than -7/del(7q), lower platelets counts compared to del(7q), higher hemoglobin levels than -7, lower absolute neutrophil counts, and higher percentage of patients with non-excess blasts (66.9% vs. 41.3%, ORs 2.374, p = 0.01) in comparison with -7/del(7q). The der(1;7) existed more as a sole karyotype aberration (55.6% vs. 37.0%, ORs 2.902, p = 0.02), co-occurred more often with +8 (22.7% vs. 4.2%, ORs 5.714, p = 0.04) whereas less -5/del(5q) (1.5% vs. 41.3%, ORs 0.040, p < 0.01) and complex karyotype (7.3% vs. 54.8%, OR 0.085, p < 0.01). The der(1;7) was associated with higher frequencies of RUNX1 (40.8% vs. 12.3%, ORs 4.764, p < 0.01), ETNK1 (28.1% vs. 2.5%, ORs 42.106, p < 0.01) and EZH2 (24.8% vs. 6.9%, ORs 3.767, p = 0.02) mutations, but less TP53 mutation (2.4% vs. 45.3%, ORs 0.043, p < 0.01). Moreover, der(1;7) patients had longer time to progression (Hazard Ratios (HRs) 0.331, p = 0.02), better overall survival (OS) than -7 patients (HRs 0.557, p < 0.01), but similar OS with del(7q) patients (HRs 0.837, p = 0.37).

Conclusion: The findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from -7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.

Keywords: cytogenetics; meta‐analysis; mutations; myelodysplastic syndrome.

FIGURE 1

The flow diagram shows the selection process used to identify relevant studies for the review and meta‐analysis.

FIGURE 2

The pooled Odds Ratios (ORs) for males and MDS with low blasts in der(1;7) patients versus − 7/del(7q) patients. (A) The forest plot shows the pooled ORs for males. (B) The forest plot shows the pooled OR for MDS with low blasts in MDS patients with der(1;7) versus with −7/del(7q). The pooled ORs and their 95% confidence interval (95% CI) were calculated using the Mantel–Haenszel method with a random‐effects model. The size of each square represents the weight of that study in the meta‐analysis. The vertical dashed line shows the pooled ORs. And the vertical solid line represents an OR of 1. The diamond represents the pooled ORs and 95% CI. If they differ from 1, the difference is considered statistically significant.

FIGURE 3

The cytogenetic and mutational profiles of der(1;7) patients and the pooled Odds Ratios (ORs) for co‐lesions in der(1;7) versus − 7/del(7q) patients. (A) The pooled frequencies of co‐occurring cytogenetic aberrations in der(1;7) patients. (B) The pooled ORs for sole chromosomal aberration, +8, complex karyotype and − 5/del(5q) in der(1;7) versus −7/del(7q) patients. (C) The pooled mutation frequencies in der(1;7) patients. (D) The pooled ORs for RUNX1, ETNK1, EZH2, TP53 and RAS pathway gene mutation in der(1;7) versus −7/del(7q) patients. RAS pathway genes include CBL, KRAS, NRAS, NF1 and PTPN11. The pooled frequencies were calculated using single‐arm meta‐analysis with an inverse variance random effects model. The pooled ORs were calculated using Mantel–Haenszel random effects meta‐analysis. The dot represents the pooled ORs, and the error bar represents 95% confidence interval. The x‐axis is on a log scale. The vertical dashed line represents an OR of 1. A p‐value <0.05 is considered statistically significant.

FIGURE 4

Better Overall Survival (OS) for der(1;7) versus − 7 and similar OS for der(1;7) and del(7q) patients. (A) The forest plot shows the Hazard Ratios (HRs) of OS in patients with der(1;7) versus −7 (B) The forest plot shows the HRs of OS in patients with der(1;7) versus del(7q). The pooled HRs were calculated using the inverse variance method with a random effects model. The diamond represents the pooled HRs and 95% CI. And the vertical solid line represents a HR of 1. If the pooled HRs and its 95% confidence interval (95% CI) are <1, indicating a lower risk of death for der(1;7) patients. If the pooled HRs and 95% CI crosses 1, indicating no significant difference in OS.

FIGURE 5

Sensitivity analyses evaluating the stability of the results. (A) The sensitivity analysis of the pooled Hazard Ratios (HRs) for overall survival (OS) in der(1;7) versus −7. (B) The sensitivity analysis of the pooled HRs for OS in der(1;7) versus del(7q). For the sensitivity analysis, the pooled HRs and 95% confidence interval of OS were recalculated after excluding each study individually.