Abstract
Objective
To evaluate differences in radiological phenotypes between B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) in pediatric patients and to assess their correlation with specific genetic alterations.
Study Design
A single-center retrospective cohort study was conducted including 144 pediatric patients (n = 115 B-ALL, n = 29 T-ALL) diagnosed with acute lymphoblastic leukemia. Comprehensive clinical, laboratory, and multi-modal imaging data (X-ray, computed tomography, magnetic resonance imaging, and ultrasonography) were analyzed. Radiological findings were correlated with molecular profiles, including KMT2A, ETV6::RUNX1, BCR::ABL1, IKZF1, and CDKN2A/B alterations. Principal outcomes included the prevalence of specific imaging features across leukemia subtypes and their association with genetic abnormalities. Statistical significance was assessed using appropriate comparative analyses.
Results
T-ALL demonstrated a more aggressive, mass-forming phenotype, with significantly higher rates of superior mediastinal widening 41.67% (n = 10) and mediastinal masses on CT 38.1% (n = 8) compared with B-ALL 12.28% (n = 14) and 2.56% (n = 2), respectively; p < 0.01. In contrast, B-ALL more frequently presented with diffuse interstitial pulmonary opacities 42.31% (n = 33). T-ALL was also associated with greater systemic and central nervous system involvement, including a higher prevalence of ischemic lesions on MRI 62.5% (n = 5) vs 24.0% (n = 12) and inguinal lymphadenopathy 37.5% (n = 3). Molecular analysis showed that KMT2A rearrangements and IKZF1 deletions were associated with disseminated disease, including pulmonary nodules and multi-organ infiltration. In B-ALL, CDKN2A/B deletions 31.3% (n = 36) were linked to hepatomegaly and inflammatory sinus changes.
Conclusion
Distinct radiological patterns differentiate the space-occupying phenotype of T-ALL from the more heterogeneous presentation of B-ALL. The observed imaging-genetic associations are promising and hypothesis-generating. Although significant results have been obtained, it is necessary to conduct prospective multicenter cohorts. A multimodal diagnostic approach is essential for accurate disease characterization and individualized management in pediatric ALL.
Keywords: pediatric acute lymphoblastic leukemia, T-ALL, B-ALL, radiology, molecular profiling, risk stratification
Introduction
Acute lymphoblastic leukemia (ALL) is the most prevalent pediatric malignancy, accounting for 28% of all childhood cancer diagnoses. Furthermore, it represents the most common form of pediatric leukemia (80%).1 In Poland, the incidence rate is 35.1 per 1,000,000 children annually. Within the pediatric population, the peak incidence occurs between 2 and 5 years of age. The most frequent subtype is B-cell precursor ALL (BCP-ALL, B-ALL), comprising approximately 85% of cases. T-cell acute lymphoblastic leukemia (T-ALL) is the second most common subtype, accounting for 12% to 15% of diagnoses.2,3
The clinical symptoms of ALL are non-specific. Children typically present with pallor, fatigue, generalised malaise, fever, and musculoskeletal pain (myalgia, bone pain, and arthralgia). Physical examination may reveal lymphadenopathy, hepatosplenomegaly, neurological deficits, testicular enlargement, and petechiae. These clinical manifestations result from bone marrow failure (anaemia, thrombocytopenia, and neutropenia). It is estimated that the interval from the onset of initial symptoms to diagnosis ranges from 2 to 6 weeks. Delays in diagnosis contribute to the late initiation of treatment; therefore, there is a critical need to refine diagnostic modalities to assess disease progression and facilitate prompt therapeutic intervention.4,5
The diagnosis of ALL is established through cytomorphological evaluation of the bone marrow (≥ 25% lymphoblasts in the aspirate) and peripheral blood cytology. A lumbar puncture for cerebrospinal fluid (CSF) analysis is mandatory to evaluate CNS infiltration. The immunophenotype (B-ALL vs T-ALL) is determined via flow cytometry (FCM). Genetic diagnostics should be completed for all patients by day 33 of treatment, utilising techniques such as somatic karyotyping, fluorescence in situ hybridisation (FISH), microarrays, and Next-Generation Sequencing (NGS).6
In BCP-ALL, specific genetic aberrations-including BCR::ABL1, KMT2A::AFF1, ETV6::RUNX1, TCF3::PBX1, TCF3::HLF, the IKZF1plus microdeletion profile, and hypodiploidy—have been identified as pivotal for risk stratification and treatment selection. In T-ALL, although numerous gene mutations and chromosomal translocations leading to aberrant gene expression have been identified, their prognostic significance remains ambiguous, and blast cell cytogenetics are not currently utilised for formal risk stratification.7 Primary imaging modalities in ALL include Radiography (X-ray), Ultrasonography (USG), Magnetic Resonance Imaging (MRI), Computed Tomography (CT), 18 F-FDG and PET/CT or PET/MRI. A baseline chest X-ray is performed on all patients. Patients with T-ALL, compared to those with B-ALL, exhibit a higher frequency of mediastinal masses and central nervous system (CNS) involvement, particularly cranial nerve palsies. Smith WT et al highlight that mediastinal masses, pleural effusions, tracheal compression, and pulmonary infiltrates are more prevalent in T-ALL than B-ALL.8 Although specific localized manifestations, such as neuro-radiological changes, have been previously addressed in the literature, and also in research involving authors of this study,9 a comprehensive approach linking whole-body imaging with immunophenotypic classifications remains lacking. The present study addresses this gap by analyzing a full panel of diagnostic radiological examinations. This study systematically classifies imaging findings according to leukemia lineages and specific genetic profiles, providing a novel diagnostic framework that is currently scarce in medical literature. Brain MRI is utilised to monitor chemotherapy-induced neurotoxicity, where periventricular white matter changes are often observed. In the evaluation of the musculoskeletal system in T-ALL patients, subperiosteal new bone formation and osteolytic lesions within the medullary cavity may be present. Radiographic abnormalities are typically localised in the long bones, most frequently the femur. Pathological fractures may also occur. MRI is superior in assessing tumor localisation, areas of necrosis, and the extent of bone marrow infiltration by blast cells.
While outcomes for T-ALL have improved in recent years with 5-year event-free survival (EFS) reaching 79% generally and exceeding 90% in highly developed countries, relapse remains the primary cause of treatment failure, affecting 13–15% of children with ALL. Notably, the management of relapsed T-ALL is associated with significantly poorer outcomes compared to B-ALL.10–12
This study was reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines (Supplementary Material 1).
Materials and Methods
The study was conducted as a single-center study. The scientific research included patients from 0 to 18 years old with confirmed diagnosis of acute lymphoblastic leukemia hospitalized from 2006 to 2023 in the Department of Pediatric Hematology, Oncology, and Transplantology of the University Children’s Hospital in Lublin. Statistical analyses were performed using the PQStat statistical package, version 1.8.4.164. The comparison of the B-ALL and T-ALL groups in terms of dichotomous qualitative scales was performed using the chi-square test and Fisher’s exact test. The comparison of the B-ALL and T-ALL groups in terms of quantitative scales was performed using the Mann–Whitney U-test and Conover’s rank variance test, after prior analysis of the normality of the distribution using the Shapiro–Wilk test. A test probability p < 0.05 was considered significant and it was judged as highly significant at p < 0.01. This study obtained approval of the Bioethics Committee of the Medical University of Lublin, KE-0254/208/10/2022. No significant missing data were identified. A complete-case analysis approach was utilized due to the high data completeness of our institutional registry Potential sources of bias related to retrospective design and imaging selection were considered. Due to the exploratory nature of this study and the comprehensive screening of multiple radiological parameters across diverse genetic subgroups, no formal a priori sample size or statistical power calculation was performed; the sample size was strictly determined by the total number of available pediatric ALL cases matching the inclusion criteria within our institutional registry over the study period. To minimise the risk of type I errors resulting from multiple clinical-radiological and molecular comparisons, the potential influence of mass significance was considered during data interpretation, and findings from subgroup analyses were treated as hypothesis-generating.
Results
A total of 115 patients with B-cell acute lymphoblastic leukemia (B-ALL) and 29 with T-cell acute lymphoblastic leukemia (T-ALL) were included in the study. The sex distribution in the analyzed groups is presented in Figure 1. No statistically significant association (p > 0.05) was found between patient sex and disease group.
Figure 1.
Sex distribution in the study groups.
The mean age at diagnosis for B-ALL was 5.92 years (± 4.4195), whereas for T-ALL it was 7.69 years (± 4.936). The age distribution between the groups did not differ significantly (p > 0.05) (Figure 2).
Figure 2.
Age distribution in the study groups.
The distribution of laboratory white blood cell (WBC) counts differed significantly between the groups (p < 0.05), with a higher median observed in the B-ALL group compared to the T-ALL group. Hemoglobin (HGB) levels did not differ significantly between the groups (p > 0.05). Platelet (PLT) counts differed significantly (p < 0.01) between the groups, with a lower median in the B-ALL group compared to the T-ALL group. Laboratory findings are presented in Figure 3.
Figure 3.
Distribution of WBC, HGB, and PLT results in the study groups.
Among all imaging studies performed, the frequency of two modalities differed significantly between the B-ALL and T-ALL groups. These included: Chest X-ray – performed in 99.13% (n=114) of patients with B-ALL and 82.76% (n=24) of patients with T-ALL, with a highly significant difference between the groups (p < 0.01).Abdominal ultrasound – performed in 69.57% (n=80) of patients with B-ALL and 48.28% (n=14) of patients with T-ALL, with a statistically significant difference between the groups (p < 0.05). For the remaining imaging studies, their frequency in both groups did not differ significantly (p > 0.05). A summary is presented in Table 1.
Table 1.
Imaging Studies Performed in the Compared Groups
| B ALL | T ALL | Test ch2 (p1=) Fisher’s Test (p2=) |
|||
|---|---|---|---|---|---|
| Abundance | Percent | Abundance | Percent | ||
| Chest X-ray | 1 | 0.87% | 5 | 17.24% | p1=0,0001 |
| 114 | 99.13% | 24 | 82.76% | p2=0,0013 | |
| Abdominal cavity X-ray | 69 | 60.00% | 20 | 68.97% | p1=0.3745 |
| 46 | 40.00% | 9 | 31.03% | p2=0.4023 | |
| Chest CT | 37 | 32.17% | 7 | 24.14% | p1=0.4012 |
| 78 | 67.83% | 22 | 75.86% | p2=0.5013 | |
| Abdominal cavity CT | 96 | 83.48% | 25 | 86.21% | p1=0.7200 |
| 19 | 16.52% | 4 | 13.79% | p2=1.0000 | |
| Head CT | 69 | 60.00% | 17 | 58.62% | p1=0.8923 |
| 46 | 40.00% | 12 | 41.38% | p2=1.0000 | |
| Nasal sinuses CT | 105 | 91.30% | 26 | 89.66% | p1=0.7818 |
| 10 | 8.70% | 3 | 10.34% | p2=0.7254 | |
| Neck CT | 114 | 99.13% | 28 | 96.55% | p1=0.2890 |
| 1 | 0.87% | 1 | 3.45% | p2=0.3633 | |
| Abdominal ultrasound | 35 | 30.43% | 15 | 51.72% | p1=0.0314 |
| 80 | 69.57% | 14 | 48.28% | p2=0.0481 | |
| Testicles ultrasound | 81 | 70.43% | 21 | 72.41% | p1=0.8340 |
| 34 | 29.57% | 8 | 27.59% | p2=1.0000 | |
| Neck with lymph nodes ultrasound | 75 | 65.22% | 23 | 79.31% | p1=0.1458 |
| 40 | 34.78% | 6 | 20.69% | p2=0.1836 | |
| Head MRI | 65 | 56.52% | 21 | 72.41% | p1=0.1189 |
| 50 | 43.48% | 8 | 27.59% | p2=0.1411 | |
| Chest scopy X-ray | 95 | 82.61% | 26 | 89.66% | p1=0.3546 |
| 20 | 17.39% | 3 | 10.34% | p2=0.5702 | |
| Thyroid gland ultrasound | 69 | 60% | 16 | 55.17% | p1=0.6366 |
| 46 | 40% | 13 | 44.83% | p2=0.6761 | |
Statistically significant differences were observed in radiological findings. On chest X-ray, superior mediastinal widening was detected in 12.28% (n=14) of B-ALL cases and 41.67% (n=10) of T-ALL cases, with a highly significant difference between the groups (p < 0.01). On chest CT, interstitial opacities were observed in 42.31% (n=33) of B-ALL cases and 9.52% (n=2) of T-ALL cases (p < 0.01). A superior mediastinal mass on chest CT was present in 2.56% (n=2) of B-ALL cases and 38.1% (n=8) of T-ALL cases (p < 0.01). Lymphadenopathy on chest CT was identified in 7.69% (n=6) of B-ALL cases and 28.57% (n=6) of T-ALL cases, with a significant difference (p < 0.05).On head CT, increased cortical sulcation was observed in 2.27% (n=1) of B-ALL cases and 36.36% (n=4) of T-ALL cases (p < 0.01). In testicular ultrasound, inguinal lymphadenopathy was not detected in the B-ALL group but was present in 37.5% (n=3) of T-ALL cases (p < 0.01). On brain MRI, ischemic lesions were observed in 24% (n=12) of B-ALL cases and 62.5% (n=5) of T-ALL cases, with a highly significant difference (p < 0.01). The frequency of KMT2A rearrangements was 6.09% (n=7) in the B-ALL group and 31.03% (n=9) in the T-ALL group (p < 0.01). The frequency of the ETV6::RUNX1 fusion was 46.09% (n=53) in B-ALL and 3.45% (n=1) in T-ALL (p < 0.01). Karyotype analysis was performed in 80% (n=92) of B-ALL patients and 10.34% (n=3) of T-ALL patients (p < 0.01). The frequency of CDKN2A deletion was 31.3% (n=36) in B-ALL and 0% in T-ALL (p < 0.01), while CDKN2B deletion occurred in 31.3% (n=36) of B-ALL cases and 3.45% (n=1) of T-ALL cases (p < 0.01).
Statistically significant associations between imaging findings and genetic alterations were identified. In T-ALL patients, interstitial opacities on chest X-ray were more frequent in those with ETV6::RUNX1 fusion (p = 0.9516; Pearson’s χ2 = 0.0037) and CDKN2B deletion (Pearson’s χ2 = 0.4859). Mediastinal widening on chest X-ray was more frequent in patients with KMT2A rearrangements (p = 0.0192; Pearson’s χ2 = 5.4857). On chest CT, pulmonary nodules were more commonly observed in patients with KMT2A rearrangements (p = 0.0494; χ2 = 3.8603). Hepatomegaly was more frequent in patients with KMT2A rearrangements on both abdominal ultrasound and CT (p = 0.018; Pearson’s χ2 = 5.6 and p = 0.0455; Pearson’s χ2 = 4, respectively). Inguinal lymphadenopathy on ultrasound was also more frequent in patients with KMT2A rearrangements (p = 0.0285; Pearson’s χ2 = 4.8).
In B-ALL patients with BCR::ABL1 fusions, superior mediastinal widening on chest X-ray (p = 0.0193), focal nodular hyperplasia (FNH)-like lesions on abdominal CT (p = 0.0001), and orchiectomy findings on testicular ultrasound (p = 0.0005) were more frequent. In patients with t(9;22) translocation, pulmonary nodules on chest CT (p = 0.0142), cortical atrophy (p = 0.0062) and asymmetric ventricular system (p = 0.0027) on brain MRI, as well as fecal retention on abdominal ultrasound (p = 0.0432), were more commonly observed. In children with KMT2A gene rearrangement, a superior mediastinal mass on chest CT (p = 0.0397) and pineal cyst on brain MRI (p = 0.0075) were more frequent. In patients with ETV6::RUNX1 fusion, subpleural infiltrates on chest X-ray (p = 0.0281) and hypodense lesions on head CT (p = 0.0281) were more common. In patients with TCF3::PBX1 fusion, features of gastrointestinal perforation on abdominal X-ray (p = 0.0082), intracranial calcifications on head CT (p = 0.0016), and pineal cyst (p = 0.0398) as well as asymmetric ventricular system (p = 0.0398) on brain MRI were more frequently observed. In patients with t(17;19)(q22;p13) translocation, hypoechoic liver lesions on abdominal ultrasound (p = 0.0336), colloid cysts in the thyroid on ultrasound (p = 0.0011), and pineal cyst (p = 0.0398) as well as an asymmetric ventricular system (p = 0.0398) on MRI were more common. In patients with IKZF1 deletion, subpleural infiltrates (p = 0.0108) and superior mediastinal mass (p = 0.0001) on chest CT, pancreatic enlargement on abdominal ultrasound (p = 0.0001), pineal cyst (p = 0.0001), arachnoid cyst (p = 0.0001), and inflammatory changes in the paranasal sinuses (p = 0.0434) on brain MRI were more frequently observed. In patients with IKZF1 mutation, ischemic lesions on head CT (p = 0.0059), hepatomegaly (p = 0.003), hypoechoic liver lesions (p = 0.0001), and lymphadenopathy (p = 0.0004) on abdominal ultrasound, as well as inflammatory changes in the paranasal sinuses on MRI (p = 0.0154), were more common. In patients with CDKN2A deletion, arachnoid cysts on head CT (p = 0.0181), hepatomegaly (p = 0.0006) and lymphadenopathy (p = 0.0063) on abdominal ultrasound, as well as arachnoid cyst (p = 0.0443) and inflammatory changes in the paranasal sinuses (p = 0.0072) on MRI were more frequent. In patients with CDKN2B deletion, arachnoid cysts on head CT (p = 0.0254), hepatomegaly on abdominal ultrasound (p = 0.0039), and arachnoid cyst (p = 0.0354) as well as inflammatory changes in the paranasal sinuses (p = 0.004) on MRI were more common. Deletion in the 11q23 region was associated with a higher frequency of ventricular system asymmetry or ventricular enlargement on head CT (p = 0.0107) and ventricular asymmetry on brain MRI (p = 0.0007).
Discussion
The radiological profile of pediatric acute lymphoblastic leukemia (ALL) represents a critical component of the diagnostic armamentarium, serving as a non-invasive strategy for early risk stratification and biological characterisation. Our comparative analysis of 115 B-cell (B-ALL) and 29 T-cell (T-ALL) patients treated in the Department of Pediatric Hematology, Oncology and Transplantology, University Children’s Hospital underscores a profound divergence in disease phenotype, where the “aggressive” T-cell signature stands in stark contrast to the more heterogeneous B-cell precursor. While clinical manifestations such as lethargy, pallor, and hematological cytopenias are ubiquitously non-specific, the radiological landscape, ranging from massive anterior mediastinal masses to subtle leukemic CNS infiltration, offers a valuable diagnostic framework to the underlying leukemogenic drivers and the systemic burden of the disease. A primary hallmark of the T-lineage immunophenotype is its dramatic and often severe intrathoracic presentation. In the present cohort, superior mediastinal widening was identified in 41.67% of T-ALL cases, compared to a marginal 12.28% in the B-ALL group. This is further corroborated by CT findings, where mediastinal masses were present in 38.1% of T-ALL patients but only 2.56% of B-ALL cases. Such findings reflect the unique biological affinity of T-lineage blasts for the thymus and paratracheal lymphatic compartments, mirroring the physiological site of T-cell maturation.13–15 These observations are not merely incidental; they dictate urgent clinical interventions to mitigate the risk of superior vena cava syndrome and mechanical tracheobronchial compression. Recognising these imaging “red flags” is clinically critical, particularly prior to procedures requiring sedation or general anesthesia, where subclinical airway narrowing can be rapidly exacerbated by the loss of physiological compensation and the relaxation of smooth muscles induced by anesthetic agents.16–20Interestingly, B-ALL patients demonstrated a distinct pulmonary phenotype characterised by diffuse interstitial opacities in 42.31% of cases, contrasting sharply with the localised, space-occupying lesions prevalent in T-ALL (9.52%). This suggests that while T-ALL tends toward localised mass formation, B-ALL lung involvement may reflect a more hematogenous, microvascular infiltration pattern.
The infiltrative capacity of T-ALL was further elucidated by its significant neuro-radiological and systemic burden. Magnetic resonance imaging (MRI) revealed a high prevalence of central nervous system (CNS) abnormalities in the T-ALL group, notably ischemic lesions in 62.5% of patients (compared to 24% in B-ALL) and increased cortical sulcation in 36.36% (versus a mere 2.27% in B-ALL). These findings align with established literature suggesting that the T-cell phenotype, often associated with hyperleukocytosis and higher metabolic demands of blast cells, carries an inherent risk for central neurotoxicity and vascular complications such as dural sinus thrombosis.21–26 Crucially, emerging neuroimaging data suggest that structural brain alterations in pediatric ALL can occur even in the absolute absence of clinically diagnosed CNS infiltration. Recent clinical evidence highlights that treatment-naive pediatric patients with new-onset ALL exhibit widespread microstructural grey matter volume reductions and white matter integrity anomalies before any therapeutic intervention. This baseline involvement is hypothesised to stem from early leukaemia-induced systemic inflammatory activation, microvascular changes, and secondary impairment of the glymphatic system. These observations strongly corroborate our findings regarding early MRI abnormalities and emphasise that subclinical neurostructural changes represent a direct manifestation of the underlying disease biology rather than exclusively therapy-induced complications.27 The transition from conventional radiography to advanced cross-sectional imaging has redefined our ability to map this extramedullary spread, with MRI remaining the gold standard for monitoring chemotherapy-induced neurotoxicity and medullary cavity replacement.28–30 The clinical relevance of establishing baseline neuroimaging profiles at diagnosis is further underscored by the known long-term neurotoxic effects of leukemia therapy. Available literature indicates that frontline chemotherapy regimens, particularly those including methotrexate, are heavily associated with white matter damage, asymptomatic leukoencephalopathy, and the degradation of microstructural brain asymmetry in pediatric ALL survivors. Given that treatment-induced neurotoxicity and myelin injury often manifest as T2-hyperintense lesions or microstructural changes in specific cerebral regions, identifying pre-existing ischemic or leukemic abnormalities through baseline MRI is essential to accurately differentiate disease-related baseline phenotypes from subsequent therapy-related central nervous system complications.31 Our findings regarding the clear phenotypic divergence between B-ALL and T-ALL closely align with reported international cohorts. For instance, literature confirms that space-occupying intrathoracic abnormalities, such as superior mediastinal widening and tracheal compression, are overwhelmingly characteristic of the T-ALL lineage due to thymic T-cell progenitor proliferation, while being exceptionally rare in B-ALL. Furthermore, the presence of these distinct imaging profiles- ranging from mediastinal masses on CT to diffuse pulmonary infiltrates-carries vital clinical implications, particularly in guiding multi-disciplinary management, optimizing anesthesia protocols to prevent airway compromise during initial diagnostic procedures, and anticipating the need for early respiratory support.10
The systemic nature of T-ALL was evidenced by the high frequency of inguinal lymphadenopathy (37.5%), a finding entirely absent in our B-ALL cohort, reinforcing the theory of a more aggressive lymphatic dissemination in this subtype.
Conversely, musculoskeletal involvement and bone marrow-related symptoms are traditionally more characteristic of B-lineage ALL. Literature indicates that bone pain and radiological bone lesions are reported in 36.3% of B-ALL cases compared to only 14.2% in T-ALL.10,32–35 This is likely due to the primary medullary origin of B-cell precursors, where the disease initiates and expands within the bone marrow environment before secondary peripheral spread. Our findings regarding the ETV6::RUNX1 fusion, present in 46.09% of B-ALL cases, support this observation, as this genetic subtype generally correlates with a more favourable biological profile and more circumscribed radiological findings compared to the infiltrative T-ALL.36–38
The most compelling aspect of our study is the strong correlation between molecular architecture and radiological phenotype, suggesting that specific genetic drivers dictate the spatial distribution of leukemic cells. We observed that the KMT2A rearrangement, occurring in 31.03% of T-ALL cases, was statistically linked to a disseminated and aggressive disease pattern, including pulmonary nodules, mediastinal masses, and hepatomegaly. Similarly, IKZF1 alterations emerged as a significant marker for advanced disease, correlating with widespread tissue infiltration involving the pancreas, subpleural spaces, and the CNS (including pineal and arachnoid cysts). In the B-ALL subgroup, specific genotypes, such as the BCR-ABL1 rearrangement and t(9;22) translocation, were associated with systemic manifestations, including cortical atrophy and changes in abdominal organs. Notably, deletions in CDKN2A and CDKN2B, identified in 31.3% of B-ALL cases, were associated with hepatomegaly and inflammatory changes in the paranasal sinuses. This suggests that these genetic lesions may influence both direct leukemic infiltration and secondary immunomodulatory or inflammatory responses in the host. The findings of this study underscore a promising correlation between molecular architecture and radiological phenotypes; however, several limitations must be acknowledged. First, the single-center, retrospective design inherently introduces selection bias and results in uneven sample sizes across specific genetic cohorts, which restricts the generalizability of the findings. Given these factors, our genotype-imaging correlations must be interpreted strictly within an exploratory framework. While our results align with emerging recent literature demonstrating that lineage-specific patterns (such as mediastinal dominance in T-ALL) and subclonal alterations distinctly influence systemic presentation, these imaging-genetic associations remain hypothesis-generating. They cannot serve as a direct surrogate for molecular risk stratification at this stage. Instead, they provide a valuable clinical framework to optimize initial multi-modal diagnostic pathways and anticipate localized complications before definitive genetic results are available. These observations emphasise that radiological evaluation provides critical, non-invasive insights into the underlying molecular abnormalities that govern disease progression and response to therapy.
Limitations
The primary limitations of this study include its single-centre design and the disproportionate sample sizes between B-ALL and T-ALL cohorts, which reflect natural epidemiological distribution but may limit statistical power for rare genetic subgroups. Further multi-centre studies are needed to confirm applicability to broader populations. Additionally, the retrospective nature of the analysis introduces potential selection bias, as imaging modalities were dictated by clinical indications rather than a standardised prospective protocol. Finally, while significant associations were identified between markers like KMT2A and IKZF1 and multi-organ involvement, these findings require further validation in larger, multi-center trials to confirm specific tissue tropism pathways.
Conclusion
In summary, our findings demonstrate that T-ALL is characterised by a predominance of mediastinal and central nervous system involvement, whereas B-ALL exhibits significant radiological heterogeneity dictated by its specific molecular subtype. The integration of high-resolution imaging features with genetic profiling, particularly the association of KMT2A and IKZF1 mutations with widespread multi-organ infiltration, provides a robust framework for improving early risk stratification. This multimodal approach, which harmonises clinical, radiological, and molecular data, is essential for achieving a precise and comprehensive understanding of pediatric ALL biology. Such synergy enables clinical teams to bridge the gap between diagnostic radiology and hematology, ultimately fostering more informed decision-making and optimised, tailored patient management from the moment of presentation to ensure the highest standards of supportive and targeted care39 The observed imaging-genetic associations are promising and hypothesis-generating; however, they require rigorous validation in larger, prospective multicenter studies with more homogenized sample sizes across lineages before routine clinical implementation.
Funding Statement
This study received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration 105 of Helsinki, and approved by the Bioethics Committee of the Medical University of Lublin KE-0254/208/10/2022.
Consent to participate. The requirement for informed consent to participate was waived by the Ethics Committee due to the retrospective design of the study.
All collected patient data were fully anonymized prior to analysis and managed in strict accordance with the ethical principles outlined in the Declaration of Helsinki and applicable personal data protection regulations.
Abbreviations
ALL, Acute Lymphoblastic Leukemia; B-ALL, B-cell Acute Lymphoblastic Leukemia; BCP-ALL, B-cell Precursor Acute Lymphoblastic Leukemia; BCR::ABL1, Breakpoint Cluster Region–Abelson 1 fusion gene; CDKN2A, Cyclin-Dependent Kinase Inhibitor 2A; CDKN2B, Cyclin-Dependent Kinase Inhibitor 2B; CNS, Central Nervous System; CSF, Cerebrospinal Fluid; CT, Computed Tomography; EFS-Event, Free Survival; ETV6::RUNX1, ETV6-RUNX1 fusion gene; FCM, Flow Cytometry; FDG, Fluorodeoxyglucose; FISH, Fluorescence In Situ Hybridisation; FNH, Focal Nodular Hyperplasia; HGB, Hemoglobin; IKZF1, Ikaros Family Zinc Finger 1 gene; KMT2A, Lysine Methyltransferase 2A gene; MRI, Magnetic Resonance Imaging; NGS, Next-Generation Sequencing; PET, Positron Emission Tomography; PET/CT, Positron Emission Tomography-Computed Tomography; PET/MRI, Positron Emission Tomography-Magnetic Resonance Imaging; PLT, Platelets; TCF3::PBX1, CF3-PBX1 fusion gene; TCF3::HLF, TCF3-HLF fusion gene; T-ALL, T-cell Acute Lymphoblastic Leukemia;USG, Ultrasound; WBC, White Blood Cells; X-ray, Radiography.
Data Sharing Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request. Due to ethical and privacy restrictions, the data are not publicly available.
Disclosure
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request. Due to ethical and privacy restrictions, the data are not publicly available.