CD146 Molecule Expression in B Cells Acute Lymphoblastic Leukemia (B-ALLs): A Flow-Cytometric Marker for an Accurate Diagnostic Workup.

Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring the t(9;22)(q34;q11)/BCR::ABL1 rearrangement represent a category with previously dismal prognosis whose management and outcome dramatically changed thanks to the use of tyrosine kinase inhibitors (TKIs) usage and more recently full chemo-free approaches. The prompt identification of these cases represents an important clinical need. Objectives: We sought to identify an optimized cytofluorimetric diagnostic panel to predict the presence of Philadelphia chromosome (Ph) in B-ALL cases by the introduction of CD146 in our multiparametric flow cytometry (MFC) panels. Methods: We prospectively evaluated a total of 245 cases of newly diagnosed B-ALLs with a CD146 positivity threshold >10% referred to the Division of Hematology of 'Sapienza' University of Rome. We compared the results of CD146 expression percentage and its mean fluorescence intensity (MFI) between Ph+ ALLs, Ph-like ALLs, and molecularly negative ALLs. Results: Seventy-nine of the 245 B-ALL cases (32%) did not present mutations at molecular testing, with 144/245 (59%) resulting in Ph+ ALL and 19/245 (8%) Ph-like ALLs. Comparing the 3 groups, we found that Ph+ B-ALLs were characterized by higher expression percentage of myeloid markers such as CD13, CD33, and CD66c and low expression of CD38; Ph+ B-ALL showed a higher CD146 expression percentage and MFI when compared with both molecular negative B-ALL and Ph-like ALLs; neither the mean percentage of CD146 expression neither CD146 MFI were statically different between molecular negative B-ALL and Ph-like ALLs. Conclusions: Our data demonstrate the association between CD146 expression and Ph+ ALLs. CD146, along with myeloid markers, may help to identify a distinctive immunophenotypic pattern, useful for rapid identification in the diagnostic routine of this subtype of B-ALLs that benefits from a specific therapeutic approach.

Bilateral Acute Proptosis With Papilledema and Sub-retinal Fluid As Initial Manifestations of Acute Lymphoblastic Leukemia in a Child.

A five-year-old boy presented with bilateral acute proptosis, papilledema, and sub-retinal fluid. Notably, choroidal thickening exceeded 600 microns. These ocular findings were the initial manifestations of acute lymphoblastic leukemia. This case underscores the importance of recognizing uncommon ocular presentations in pediatric leukemia for timely diagnosis and management.

Molecular pathology and computational profiling of Janus kinase 2 (JAK2) mutation in acute lymphoblastic leukemia: insights from a Pakistani cohort.

BACKGROUND: JAK2 mutation plays a clinically significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) by enhancing its oncogenicity. The study aimed to characterize the molecular pathology and computational profile of the JAK2 mutation in an ALL cohort of Pakistani origin. METHODS: Ninety-three patients were enrolled in the current study. The disease diagnosis was confirmed via flow cytometry and karyotyping of bone marrow aspirate/blood. For the identification of causative gene variations and assessment of their potential impact, the JAK2 gene underwent direct sequencing and predictive computational and in silico structural analysis, respectively. RESULTS: JAK2 mutations were detected in 10 (11%) patients. All mutations were missense with 1 being frameshift. Most mutations showed a similar pattern to the wild type but p.N673H+p.V674L+p.C675W (AAD699), p.V674F (AAD704), and p.V674L (AAD705) exhibited statistically significant stability loss. The triple mutation displayed reduced stability both globally and locally. CONCLUSION: The pattern of gene defects in JAK2 in the studied cohort showed a disruption in proper folding behavior, evident from increased gyration values, resulting in the hypothesis that these mutations may cause structural alterations in the JAK2 protein that lead to disease progression.

A Chronological Overview of Using Deep Learning for Leukemia Detection: A Scoping Review.

Leukemia is a rare but fatal cancer of the blood. This cancer arises from abnormal bone marrow cells and requires prompt diagnosis for effective treatment and positive patient prognosis. Traditional diagnostic methods (e.g., microscopy, flow cytometry, and biopsy) pose challenges in both accuracy and time, demanding an inquisition on the development and use of deep learning (DL) models, such as convolutional neural networks (CNN), which could allow for a faster and more exact diagnosis. Using specific, objective criteria, DL might hold promise as a tool for physicians to diagnose leukemia. The purpose of this review was to report the relevant available published literature on using DL to diagnose leukemia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles published between 2010 and 2023 were searched using Embase, Ovid MEDLINE, and Web of Science, searching the terms "leukemia" AND "deep learning" or "artificial neural network" OR "neural network" AND "diagnosis" OR "detection." After screening retrieved articles using pre-determined eligibility criteria, 20 articles were included in the final review and reported chronologically due to the nascent nature of the phenomenon. The initial studies laid the groundwork for subsequent innovations, illustrating the transition from specialized methods to more generalized approaches capitalizing on DL technologies for leukemia detection. This summary of recent DL models revealed a paradigm shift toward integrated architectures, resulting in notable enhancements in accuracy and efficiency. The continuous refinement of models and techniques, coupled with an emphasis on simplicity and efficiency, positions DL as a promising tool for leukemia detection. With the help of these neural networks, leukemia detection could be hastened, allowing for an improved long-term outlook and prognosis. Further research is warranted using real-life scenarios to confirm the suggested transformative effects DL models could have on leukemia diagnosis.

[Experience with an international study on standard-risk relapsed childhood acute lymphoblastic leukemia (IntReALL SR 2010 study) in Japan].

Many effective new agents for relapsed childhood acute lymphoblastic leukemia (ALL) are now becoming available, and international standard chemotherapy should be developed to optimize use of these agents. Randomized controlled trials (RCTs) are needed to establish a standard treatment, but few have been conducted for relapsed childhood ALL in Japan due to the small patient population. Participation in international RCTs is necessary to access sufficient patients for informative study results, but differences in approved drugs and healthcare systems between countries make this challenging. In 2014, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) participated in an international study on standard-risk relapsed childhood ALL (IntReALL SR 2010) involving two RCTs and multiple drugs not approved in Japan, which was addressed by replacing the unapproved drugs with alternative approved drugs with the same or similar efficacy. This article discusses the historical background of treatment development for relapsed childhood ALL, our experience in participating in the IntReALL SR 2010 trial, and prospects for treating relapsed childhood ALL.

Acute Pancreatitis Caused by Pegylated (PEG)-Asparaginase Associated With Severe Hypertriglyceridemia.

Pegylated (PEG)-asparaginase is used during the induction and intensification phases of treatment for B-cell acute lymphoblastic leukemia (B-ALL). It works by depleting the external sources of asparagine, causing the death of lymphoblasts. It has several adverse effects, including pancreatitis and hypertriglyceridemia; however, the simultaneous occurrence of both is uncommon. We present the case of an 18-year-old man with B-ALL who developed acute epigastric pain radiating to the back and non-bloody, non-bilious emesis following treatment with PEG-asparaginase. He was diagnosed with acute interstitial pancreatitis and severe hypertriglyceridemia. Conservative management was used for the pancreatitis, while hypertriglyceridemia was treated with an insulin infusion. Pancreatic toxicity and hypertriglyceridemia can necessitate the discontinuation of PEG-asparaginase, limiting treatment options and potentially increasing the risk of relapse. Therefore, further studies are needed to identify the factors contributing to hypertriglyceridemia and pancreatitis, aiding clinicians in monitoring and prevention.

Spontaneous Remission of Acute Lymphoblastic Leukemia Following Candida tropicalis Fungemia.

Spontaneous remission (SR) in acute lymphoblastic leukemia (ALL) is a poorly understood phenomenon that has been sporadically reported in medical literature for over a century, and the molecular and immunologic mechanisms of remission pose interesting clinical questions. Furthermore, the often-transient nature of these remissions poses a challenge to physicians in formulating an approach to treatment. We report on a rare case of Candida tropicalis sepsis in a three-year-old female with high-risk ALL who received less than two months of treatment prior to sepsis and subsequent SR.

Diffuse large B-cell lymphoma with central nervous system symptoms during the maintenance therapy of acute lymphoblastic leukemia: a case report and literature review.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) secondary to acute lymphoblastic leukemia (ALL) is a rare disease with poor prognosis, usually attributed to delayed diagnosis. To date, only four cases of ALL developing DLBCL have been reported, while none of them exhibiting central nervous system (CNS) symptoms. CASE DESCRIPTION: Here, we report an unusual case of a 15-year-old boy diagnosed with ALL and treated based on the SCCLG-ALL 2016 protocol. While he was receiving maintenance treatment, the patient developed dizziness and vomiting. An Epstein-Barr virus (EBV)-positive DLBCL with CNS involvement was diagnosed from inguinal lymph nodes biopsy, EBV DNA tests and head magnetic resonance imaging (MRI). Meanwhile, a dramatic decrease of immune cells and immunoglobulin was detected in the occurrence of DLBCL. He received therapy based on SCCCG-NHL-2017 protocol immediately after the diagnosis. CONCLUSIONS: We present the first retrospective report of four cases of non-Hodgkin lymphoma (NHL) secondary to ALL between 1990 and 2022. The pathogenesis of secondary DLBCL may be related to infection, immunodeficiency, genetic susceptibility, and treatment. Thus, the detection of EBV DNA during the full course of ALL therapy and genetic tests were needed in the occurrence of secondary DLBCL. Given to the rare rate and insufficient treatment experience, longer follow-up and enough sample size are needed.

Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients.

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients' characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Clcr) for volume of distribution (Vd). A significant difference was found in Scr, Clcr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted.

Different Levels of Therapeutic Strategies to Recover the Microbiome to Prevent/Delay Acute Lymphoblastic Leukemia (ALL) or Arrest Its Progression in Children.

Changes in the components, variety, metabolism, and products of microbiomes, particularly of the gut microbiome (GM), have been revealed to be closely associated with the onset and progression of numerous human illnesses, including hematological neoplasms. Among the latter pathologies, there is acute lymphoblastic leukemia (ALL), the most widespread malignant neoplasm in pediatric subjects. Accordingly, ALL cases present a typical dysfunctional GM during all its clinical stages and resulting inflammation, which contributes to its progression, altered response to therapy, and possible relapses. Children with ALL have GM with characteristic variations in composition, variety, and functions, and such alterations may influence and predict the complications and prognosis of ALL after chemotherapy treatment or stem cell hematopoietic transplants. In addition, growing evidence also reports the ability of GM to influence the formation, growth, and roles of the newborn's hematopoietic system through the process of developmental programming during fetal life as well as its susceptibility to the onset of onco-hematological pathologies, namely ALL. Here, we suggest some therapeutic strategies that can be applied at two levels of intervention to recover the microbiome and consequently prevent/delay ALL or arrest its progression.

Characterization of brain development with neuroimaging in a female mouse model of chemotherapy treatment of acute lymphoblastic leukemia.

Background: Survivors of pediatric acute lymphoblastic leukemia (ALL) exhibit abnormal neurocognitive outcomes that are possibly due to exposures to neurotoxic chemotherapy agents. This study aimed to determine the feasibility of characterizing long-term neuroanatomical changes with in vivo neuroimaging in a preclinical model of treatment for ALL. Methods: Female mice (C57BL/6) were randomly assigned to a saline control group (n=10) or a treatment group (n=10) that received intrathecal methotrexate and oral dexamethasone (IT-MTX + DEX). Mice were subsequently scanned three times on a 7T MRI at ages 3, 6, and 12 months (T1, T2, and T3, respectively), which corresponds with human age-equivalents spanning early to late adulthood. Regional brain volumes were automatically segmented, and volume change between timepoints (i.e., T1 to T2; and T2 to T3) were compared between groups (i.e., saline vs. IT-MTX + DEX). Results: Five mice in the IT-MTX + DEX group, and seven mice in the saline group completed all three scans. Between T1 and T2, volumetric change was significantly different between groups in total gray matter [estimate =2.06, 95% confidence interval (CI): 0.27-3.84], the cerebrum (estimate =1.62, 95% CI: 0.14-3.09), claustrum (estimate =0.06, 95% CI: 0.02-0.09), amygdala (estimate =0.16, 95% CI: 0.03-0.29), and striatum (estimate =0.18, 95% CI: 0.01-0.35), with the IT-MTX + DEX group exhibiting a more robust increase in volume than the saline-treated group. Between T2 and T3, group differences in structural brain development were evident for total white matter (estimate =-0.14, 95% CI: -0.27 to -0.01), and the corpus callosum (estimate =-0.09, 95% CI: -0.19 to 0.00) and amygdala (estimate =-0.05, 95% CI: -0.10 to 0.00). In contrast to the rapid brain growth observed earlier in development (i.e., T1 to T2), the IT-MTX + DEX group exhibited an attenuated increase in volume relative to the saline-treated group between T2 and T3. Conclusions: The results demonstrate feasibility of modeling pediatric ALL treatment in a preclinical model and highlight the potential of using preclinical neuroimaging models to gain insight into brain development throughout survivorship.

Impact of the COVID-19 pandemic on utilization and cost for care of pediatric and young adult ALL.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and among the most common malignancies in young adults and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood and young adult ALL in regard to utilization and cost of care among commercially insured individuals in the United States. RESULTS: Utilizing a commercial insurance claims database, 529 pediatric and young adult patients were identified who were diagnosed with ALL between January 2016 and March 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost during the initial 8 months of therapy. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric and young adult ALL was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric and young adult populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric and young adult cancer.

Hemorrhagic Posterior Reversible Encephalopathy Syndrome in a Pediatric Patient With Acute Lymphoblastic Leukemia: A Case Report.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon yet severe neurological disorder characterized by a combination of clinical and radiological features. Common clinical presentations of PRES include headaches, seizures, altered mental status ranging from lethargy to coma, visual disturbances, and behavior changes.  This case report outlines the occurrence of hemorrhagic PRES in an 11-year-old girl with B-cell acute lymphoblastic leukemia (ALL) relapse. Hospitalized for ALL relapse, the patient underwent reinduction chemotherapy. On the ninth day of admission, she had a generalized tonic-clonic seizure with a blood pressure peak of 170/120 mmHg. Magnetic resonance imaging (MRI) and a seizure episode suggested PRES. Initially, after the first tonic-clonic seizure, the neurological examination was normal, but after the second seizure, the meningeal symptoms were negative, and gaze palsy and right-sided homonymous hemianopsia were observed; muscle strength was symmetrically reduced in the upper and lower extremities and reflexes were symmetrical and diminished. A bilateral Babinski reflex was observed at the time of examination; the patient had mild motor aphasia, and she opened her eyes only in response to tactile stimulation. A follow-up MRI four days after the second seizure episode showed extensive PRES damage with hemorrhagic changes. Over two weeks, the patient's neurological status and blood pressure gradually improved, with persistent changes in the visual field. Subsequent MRI revealed a significant reduction in PRES lesions, but residual hemorrhage measuring 6x4 cm remained evident.

Outcomes and adverse events in older acute lymphoblastic Leukemia patients treated with a pediatric-inspired protocol with Pegylated or native Asparaginase.

This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.

The Potential Role of NOD2/CARD15 Genotype as a Prognostic Indicator for Bone Marrow Transplantation Outcomes in Patients With Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Systematic Review.

Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholar articles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study. Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survival and increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.

Design, synthesis, and pharmacological evaluation of novel benzothiazole derivatives targeting LCK in acute lymphoblastic leukemia.

Lymphocyte-specific protein tyrosine kinase (LCK), a member of the Src family of tyrosine kinases, is implicated in the pathogenesis of almost all types of leukemia via T cells activation and signal transduction. LCK is highly expressed in acute lymphoblastic leukemia (ALL), and knockdown of the LCK gene can significantly inhibit the proliferation of leukemia cell lines. Here, we designed and synthesized a series of benzothiazole derivatives as novel LCK inhibitors using both docking-based virtual screening and activity assays for structural optimization. Among these compounds, 7 m showed a strong inhibitory activity in the proliferation of leukemia cell lines and LCK kinase activity. Moreover, we found that compound 7 m could induce apoptosis while simultaneously blocking cell cycle via decreasing its phosphorylation at Tyr394 of the LCK. Collectively, these findings shed new light on compound 7 m that would be utilized as a promising drug candidate with apoptosis-triggered and cell cycle arrest activities for the future ALL therapy.

A surrogate molecular approach for the detection of Philadelphia chromosome-like B-acute lymphoblastic leukemia.

BACKGROUND: Philadelphia chromosome (Ph)-like B-acute lymphoblastic leukemia (B-ALL) is a clinically significant, high-risk genetic subtype of B-ALL cases. There are few data on the incidence, characterization, and treatment outcomes of Ph-like ALL cases from low- and middle-income countries. There is a pressing need to establish a well-organized/cost-effective approach for identifying Ph-like ALL instances. METHODS: Multiplex reverse transcriptase polymerase chain reaction, nCounter NanoString, and fluorescence in situ hybridization were used to detect and characterize Ph-like ALL cases among recurrent genetic abnormalities (RGA)neg B-ALL cases. At the end of induction therapy, flow cytometry-minimal residual disease (MRD) assay was used to quantify MRD positivity in Ph-like ALL cases. RESULTS: Of 130 newly diagnosed B-ALL cases, 25% (BCR::ABL1), 4% (ETV6::RUNX1), 5% (TCF3::PBX1), 2% (KM2TA::AFF1), and 65% RGAneg B-ALL cases were revealed by multiplex reverse transcriptase polymerase chain reaction. Among RGAneg B-ALL cases, 24% Ph-like ALL cases using nCounter NanoString were identified, with 48% CRLF2high cases with 45% CRLF2::P2RY8 and 18% CRLF2::IGH rearrangements(∼r) revealed by fluorescence in situ hybridization. In 52% of CRLF2low cases, 17% ABL1 and JAK2∼r 8% EPOR::IGH & PDGRFB∼r were identified. Ph-like ALL cases had higher total leukocyte count (p < .05), male preponderance (p < .05), and high MRD-positivity/induction failure compared with RGAneg B-ALL cases. Furthermore, in Ph-like ALL cases, 11 significant genes using quantitative polymerase chain reaction were identified and validated. CRLF2, IGJ, CEACAM6, MUC4, SPATS2L and NRXN3 genes were overexpressed and show statistical significance (p < .05) in Ph-like ALL cases. CONCLUSIONS: This study showed the high incidence of Ph-like ALL cases with kinase activating alterations and treatment outcomes from low- and middle-income region. Furthermore, a surrogate cost-effective multiplex panel of 11 overexpressed genes for the prompt detection of Ph-like ALL cases is proposed. PLAIN LANGUAGE SUMMARY: Identification of recurrent gene abnormalities (RGA)neg B-acute lymphoblastic leukemia (B-ALL) cases using multiplex-reverse transcriptase polymerase chain reaction. Identification and characterization of Philadelphia (Ph)-like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization. Furthermore, Ph-like ALL cases were characterized according to CRLF2 expression and kinase-activating genomic alterations. Minimal residual disease of Ph-like ALL cases were quantified using flow cytometry-minimal residual disease assay. A surrogate molecular approach was established to detect Ph-like ALL cases from low- and middle-income countries.