S-AML is a heterogeneous disease that increases in frequency with age, remains a challenge to therapy[14]. Myelodysplastic syndrome (MDS) is characterized by cytopenia, osteomyelodysplasia, hematopoietic dysfunction, and a high risk of transition to AML[15]. More than half of the S-AML patients reported in this study converted from MDS to AML. Compared with primary AML patients, S-AML patients have worse clinical prognosis, including complete remission rate (CR), recurrence free survival rate and OS rate[16]. Our previous study showed that abnormal increase of peripheral blood regular T cells (Treg) cells may cause the imbalance of immune status of S-AML patients, which may be relevant to poor chemotherapy effect and short survival time of S-AML patients[17]. It has been reported in the literature that there are tumor suppressor genes on chromosome 6q, 7p, 10p, 11q, 14q and 20q, which play an important role in the transformation from MDS to AML[18]. Chromosomes are associated with the progression of S-AML patients, and deserved further study. The purpose of this study was to analyze the chromosome karyotype results of S-AML patients and further explore the factors connected with survival and prognosis of S-AML patients in combination with relevant laboratory examinations.
Our results indicated that most S-AML patients had abnormal chromosome karyotype, including autosomal and sex chromosomal abnormalities. Abnormal changes of autosomal karyotypes were more common in S-AML patients and were closely related to survival prognosis. Studies have shown a more incidence of abnormalities on chromosomes 5 and 7 in patients with S-AML[19, 20]. In our study, 62.5% (10/16) abnormal chromosome karyotypes had abnormalities on chromosomes 5 and 7. Admittedly, our data are limited and we do not have much information based on the results of only 26 S-AML patients. Abnormal changes of sex chromosomes have been rarely reported in myeloid malignancies[21]. We found an extra sex chromosome (X chromosome) in a FAB-M4 patient who was transformed from MDS in an elderly woman, and the abnormal chromosome karyotypes were: 48,XXX,del(20)(q13),+X,+marker.[8]/48,XX,del(20)(q13),+14,+marker.[3]. The patient was still alive. We also detected Y chromosome deletion in an elderly male patient with AML transformed by MDS, and the abnormal karyotype was: 43,X,t(5;19)(q21;q13),7q+,-7,-12,-20,-Y,+marker.[7]/44,XY,5q-,7q+,-12,-18,-20,+marker1,+marker2.[13]. Unfortunately, the patient lost to follow-up, and we couldn't know whether the patient lives or dies. Some studies have suggested that Y chromosome loss is an age-related phenomenon with no prognostic significance[22]. Studies have shown that sex chromosome loss increases with age, and that Y chromosome loss reduces the risk of converting MDS patients to leukemia[23]. Loss of X chromosome may be associated with a better prognosis in female AML patients with t (8;21), and loss of Y chromosome may be associated with a high level of recurrence rate in men AML patients with t (8:21)[24]. The relationship between sex chromosome abnormality and survival in S-AML patients needs to be further explored by expanding the data.
LDH not only plays an important role in the early diagnosis and prognosis of many solid tumors, but also plays an important part in evaluating the severity of leukemia patients[25, 26]. LDH is positively correlated with tumor burden and is an independent prognostic factor for early death in hyperleukocytic AML[27]. Compared with the normal karyotype group, our results showed that LDH levels were significantly increased in the abnormal karyotype group. It suggested that the higher LDH level in S-AML patients, the greater the tumor burden, the greater the possibility of chromosomal karyotype abnormality, and the worse the OS rate. To conclude, abnormalities of LDH and chromosomal karyotypes are closely related to the severity and survival prognosis of S-AML patients, which may be a very valuable indicator for further risk stratification of S-AML in the future.
Most AML patients with chromosome number abnormalities may be manifested by an increase of 1–2 chromosomes (47–48 chromosomes), known as low hyperdiploid, and rare high hyperdiploidy (49–65 chromosomes), both of which are associated with poor outcome in AML[28–30]. It has also been reported that there was no difference in 5-yaar OS and EFS between AML patients with non-hyperdiploid and hyperdiploid karyotypes (48–65 chromosomes)[31]. Hypodiploidy (< 46 chromosomes) has been reported mostly in acute lymphoblastic leukemia (ALL), but rarely in AML[32–34]. However, there is currently lack of further research on the prognosis of survival in S-AML patients with hyperdiploid or hypodiploid. In addition to other factors affecting OS, such as various treatment regimens, our research found that chromosome karyotype were closely relevant to the survival of S-AML patients, and patients with abnormal chromosomal karyotypes demonstrated inferior OS compared with those normal chromosomal. What’s more, S-AML patients with hypodiploid showed worse outcome than those with hyperdiploid.
There are some limitations in our study. Firstly, the abnormality of sex chromosomes may be related to the survival prognosis of S-AML, but no definite conclusion could be drawn because of the small number of sex chromosome abnormalities in our study. Apart from this, the accurate information of all patients could not be obtained through telephone follow-up in this study, which may interfere with the experimental results. Additionaly, this study is a single-center retrospective study, and the number of included cases is relatively small, so it needs to further expand the sample size for study. Moreover, with the heterogeneity of the individualized treatment among AML patients, treatment regimens would constitute an important source of limitation, which may have exerted some influence on the results.
In conclusion, our reaearch highlights the contribution of chromosomes, as well as LDH, leading to poor prognosis of S-AML, and the abnormity of sex chromosomes may be associated with the survival prognosis of S-AML patients. Understanding the multifactorial contributions will lead to more precise risk classification and treatment strategies. More factors related to the survival and prognosis of S-AML need to be explored, which may contribute to monitoring the progression of the disease, early diagnosis and treatment.