Acute lymphoblastic leukemia

Acute leukemia evolving from an underlying MDS with del(5q) is almost always of myeloid lineage and only anecdotal case reports of MDS transforming to ALL have been reported (Agostino et al., 2011; Jain et al., 2016). Whether the presence of del(5q) in these cases reflects the underlying myelodysplastic state that later evolved into ALL remains unclear. del(5q) in ALL is mostly associated with multiple cytogenetic abnormalities that thought to be due to clonal expansion from an abnormal pluripotent stem cell.

At least 160 reported patients aged 0 to 86 years (98 males, 61 females, 1 unknown); prevalence of pediatric patients (86 patients) and there were 46 adults.
B-cell acute lymphoblastic leukemia: 70 patients aged 0 to 86 years (41 males and 28 females, 1 unknown); among them there were 22 adults (14 males and 8 females, aged 22 to 86 years; median 42 years) and 39 pediatric patients (22 males and 17 females, aged 0 to 18; median 6 years). In addition, there were 9 patients with unknown age (5 males and 3 females, 1 unknown).
T-cell acute lymphoblastic leukemia: 58 patients (35 males and 23 females aged 1 to 79 years); among them there were 17 adults (9 males and 8 females aged 19 to 79 years), 35 pediatric patients (22 males 13 females aged 1 to 18 years) and 6 patients with unknown age (4 males and 2 females).
32 patients had unspecified ALL (22 males, 10 females aged 3 to 81 years; median 13 years); 7 patients were adults (5 males and 2 females) aged 34 to 81 years (median 72 years), 12 were pediatric patients (8 males and 4 females aged 3 to 16 years; median 6 years) and there were 12 patients with unknown age (8 males and 4 females).

In contrast to its presence in myeloid malignancies, isolated del(5q) is rare in ALL, thus its clinical significance is unknown. del(5q) also appears to be clinically insignificant in patients following cytotoxic therapy or tyrosine kinase inhibitor (TKI) therapy, similar to other clonal cytogenetic abnormalities if detected as a minor clone (Tang et al., 2015). del(5q) in ALL mainly found as a clonal evolution event associated with disease progression.

Del(5q) may be found as sole abnormality at first, as an evolutionary event in other cases, and as a transient event in patients after being treated with cytotoxic agents or TKI for the prior malignancies.

Interstitial or terminal deletions of the long arm of chromosome 5 are common findings in MDS or acute myeloid leukemia (AML), but they may also occur in patients with ALL. Deletions of genetic material from 5q result in loss of tumor suppressor genes that may potentially play a role in the pathogenesis of these diseases. The long arm of chromosome 5 contains many genes that are relevant in hematopoiesis and several candidate genes including transcription factors, cytokines and their receptors, signal mediators and cell cycle regulators have been identified. These include the RPS14 gene on 5q33.1, a critical gene for the erythroid phenotype, a microRNA cluster on 5q32-33 important for the megakaryocytic phenotype, the EGR1 gene on 5q31 that plays a role in hematopoietic stem cell proliferation. Other genes such as NPM1 and APC, the transcription factor Egr1/Krox20, the cytoskeletal remodeling protein, alpha-catenin may also contribute to the disease phenotype and progression (Tang et al., 2015). Although a critical tumor suppressor gene has not yet been identified in ALL, several putative tumor suppressors such as NR3C1 and TCF7, located within the 5q31 common deleted region and TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, mapping at 5q35 have been found to be down-regulated in T- ALL (La Starza et al.,2016). Given the large size and variable pattern of 5q deletions, it is probable that the loss of several genes that act alone or in combination contribute to pathogenesis. The absence of a clear critical gene suggests that deletion of variable combinations of genes may result in a clinical spectrum ranging from myeloid malignancies to lymphoid leukemia.