Postnatal outcome following fetal aortic valvuloplasty for critical aortic stenosis.

OBJECTIVE: To report our experience of fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS), with a focus on the postnatal evolution of the patients. METHODS: This was a retrospective study including all fetuses with critical AS which underwent FAV in a single center between January 2011 and June 2022. FAV was performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the antegrade aortic flow across the aortic valve. At birth, a biventricular circulation (BVC) strategy was decided assuming the left ventricular (LV) systolic and diastolic function would ensure the systemic circulation. RESULTS: Sixty-three FAV procedures were performed in 58 fetuses, at a median (range) gestational age of 26.2 (20.3-32.2) weeks. The procedure was technically successful in 50/58 (86.2%) fetuses. There were 11/58 (19.0%) cases of in-utero demise and 9/58 (15.5%) terminations of pregnancy. No patient was liveborn after an unsuccessful procedure. Thirty-eight (65.5%) infants were liveborn, at a median (range) gestational age of 38.1 (29.0-40.6) weeks, of whom 21 (55.3%) required prostaglandin treatment. Twenty-eight of the 38 (73.7%) liveborn children (48.3% of the study population) entered the BVC pathway at birth. Among them, 20 (71.4%) required an aortic valvuloplasty procedure at birth (11 (55.0%) percutaneous balloon, nine (45.0%) surgical) and eight (28.6%) did not require any treatment at birth, but, of these, five (62.5%) underwent surgical valvuloplasty between day 26 and day 1200 of age. Eleven (39.3%) of the infants with BVC at birth required a second intervention and four (14.3%) of them required a third intervention. Two (7.1%) infants who entered the BVC pathway at birth underwent conversion to univentricular circulation (UVC). None of the surviving children with BVC developed pulmonary hypertension. The overall survival rate in those with BVC at birth was 22/28 (78.6%) at a median (range) follow-up of 23.3 (2.0-112.6) months. Ten of the 58 (17.2%) patients had UVC at birth. Among these, six (60.0%) received compassionate care from birth and four (40.0%) underwent surgery. Three of the 10 patients who had UVC at birth were still alive at the latest follow-up assessment, at a median (range) gestational age of 24.3 (8.3-48.7) months. CONCLUSIONS: FAV for critical AS led to increase of antegrade aortic flow in 86.2% of fetuses, with BVC being achieved in 48.3% (73.7% of the liveborn cases). Among patients with BVC at birth, the rate of reintervention was high, but 78.6% of these children were alive at the latest evaluation. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Activation of the receptor tyrosine kinase RET improves long-term hematopoietic stem cell outgrowth and potency.

Expansion of human hematopoietic stem cells (HSCs) is a rapidly advancing field showing great promise for clinical applications. Recent evidence has implicated the nervous system and glial family ligands (GFLs) as potential drivers of hematopoietic survival and self-renewal in the bone marrow niche; how to apply this process to HSC maintenance and expansion has yet to be explored. We show a role for the GFL receptor, RET, at the cell surface of HSCs in mediating sustained cellular growth, resistance to stress, and improved cell survival throughout in vitro expansion. HSCs treated with the key RET ligand/coreceptor complex, glial-derived neurotrophic factor and its coreceptor, exhibit improved progenitor function at primary transplantation and improved long-term HSC function at secondary transplantation. Finally, we show that RET drives a multifaceted intracellular signaling pathway, including key signaling intermediates protein kinase B, extracellular signal-regulated kinase 1/2, NF-κB, and p53, responsible for a wide range of cellular and genetic responses that improve cell growth and survival under culture conditions.

Accuracy and impact of prenatal diagnosis of common arterial trunk.

OBJECTIVES: Outcome of common arterial trunk (CAT) depends mainly on truncal valve function, presence of coronary artery abnormalities and presence of interrupted aortic arch. The main objective of this study was to evaluate the accuracy of prenatal diagnosis of CAT by analyzing prenatal vs postnatal assessment of: (1) anatomic subtypes and (2) truncal valve function. The secondary objective was to assess the potential impact of prenatal diagnosis of CAT on postnatal mortality and morbidity by comparing prenatally vs postnatally diagnosed patients. METHODS: This was a retrospective analysis of all CAT patients diagnosed either prenatally, with postnatal or fetopsy confirmation, or postnatally, from 2011 to 2019 in a single tertiary center. Cohen's kappa statistic was used to evaluate agreement between pre- and postnatal assessment of anatomic subtypes according to Van Praagh and of truncal valve function. Mortality and morbidity variables were compared between prenatally vs postnatally diagnosed CAT patients. RESULTS: A total of 84 patients (62 liveborn with prenatal diagnosis, 16 liveborn with postnatal diagnosis and six terminations of pregnancy with fetopsy) met the inclusion criteria. The accuracy of prenatal diagnosis of CAT anatomic subtype was 80.3%, and prenatal and postnatal concordance for subtype diagnosis was only moderate (κ = 0.43), with no patient with CAT Type A3 (0/4) and only half of patients with CAT Type A4 (8/17) being diagnosed prenatally. Fetal evaluation of truncal valve function underestimated the presence (no agreement; κ = 0.09) and severity (slight agreement; κ = 0.19) of insufficiency. However, four of five cases of postnatally confirmed significant truncal valve stenosis were diagnosed prenatally, with fair agreement for both presence and severity of stenosis (κ = 0.38 and 0.24, respectively). Mortality was comparable in patients with and those without prenatal diagnosis (log-rank P = 0.87). CAT patients with fetal diagnosis underwent earlier intervention (P < 0.001), had shorter intubation time (P = 0.047) and shorter global hospital stay (P = 0.01). CONCLUSIONS: The accuracy of prenatal diagnosis of CAT is insufficient to tailor neonatal management and to predict outcome. Fetal assessment of truncal valve dysfunction appears unreliable due to perinatal transition. Improvement is necessary in the fetal diagnosis of anatomic subtypes of CAT requiring postnatal prostaglandin infusion. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Reliability of Peak Exercise Stroke Volume Assessment by Impedance Cardiography in Patients with Residual Right Outflow Tract Lesions After Congenital Heart Disease Repair.

Global ventricular response to exercise may be useful in follow-up of patients with residual right outflow tract lesions after congenital heart disease repair. In this context, impedance cardiography is considered accurate for stroke volume (SV) measurement during exercise testing, however, to date, only partial assessment of its reliability has been reported. We retrospectively evaluated relative and absolute reliability of peak SV by impedance cardiography during exercise using intraclass correlation (ICC) and standard error of measurement (SEM) in this population. Peak SV was measured in 30 young patients (mean age 14.4 years ± 2.1) with right ventricular outflow tract reconstruction who underwent two cardiopulmonary exercise tests at a mean one-year interval. SV was measured using a signal morphology impedance cardiography analysis device (PhysioFlow®) and was indexed to body surface area. ICC of peak indexed SV measurement was 0.80 and SEM was 10.5%. High heterogeneity was seen when comparing patients according to peak indexed SV; in patients with peak SV < 50 ml/m2 (15 patients), ICC rose to 0.95 and SEM dropped to 2.7%, while in patients with a peak SV > 50 ml/m2 relative and absolute reliability decreased (ICC = 0.45, SEM = 12.2%). Peak exercise SV assessment by a PhysioFlow® device represents a highly reliable method in patients with residual right outflow tract lesions after congenital heart disease repair, especially in patients with peak SV < 50 ml/m2. In this latter group, a peak SV decrease > 7.3% (corresponding to the minimum "true" difference) should be considered a clinically-relevant decrease in global ventricular performance and taken into account when deciding whether to perform residual lesion removal.

Significant Change in Marine Plankton Structure and Carbon Production After the Addition of River Water in a Mesocosm Experiment.

Rivers are known to be major contributors to eutrophication in marine coastal waters, but little is known on the short-term impact of freshwater surges on the structure and functioning of the marine plankton community. The effect of adding river water, reducing the salinity by 15 and 30%, on an autumn plankton community in a Mediterranean coastal lagoon (Thau Lagoon, France) was determined during a 6-day mesocosm experiment. Adding river water brought not only nutrients but also chlorophyceans that did not survive in the brackish mesocosm waters. The addition of water led to initial increases (days 1-2) in bacterial production as well as increases in the abundances of bacterioplankton and picoeukaryotes. After day 3, the increases were more significant for diatoms and dinoflagellates that were already present in the Thau Lagoon water (mainly Pseudo-nitzschia spp. group delicatissima and Prorocentrum triestinum) and other larger organisms (tintinnids, rotifers). At the same time, the abundances of bacterioplankton, cyanobacteria, and picoeukaryote fell, some nutrients (NH4+, SiO43-) returned to pre-input levels, and the plankton structure moved from a trophic food web based on secondary production to the accumulation of primary producers in the mesocosms with added river water. Our results also show that, after freshwater inputs, there is rapid emergence of plankton species that are potentially harmful to living organisms. This suggests that flash flood events may lead to sanitary issues, other than pathogens, in exploited marine areas.

Clinical course and outcome of antenatally detected atrioventricular block: experience of a single tertiary centre and review of the literature.

OBJECTIVE: The objective is to study the course and outcome of fetuses with congenital atrioventricular block (AVB) in a single centre. METHODS: Retrospective analysis of cases diagnosed prenatally with second and third degree AVB. The clinical characteristics and outcome of fetal AVB were evaluated including in utero treatment. RESULTS: Sixty-two cases were studied. AVB was associated with a congenital heart defect (CHD-AVB) in 17 cases (27%), whereas it was isolated (i-AVB) in 45 (73%), 42 of which were associated with maternal antibodies. There were nine (52.9%) live births in the CHD-AVB group, five of which (55%) resulted in infant deaths. In the i-AVB group, there were 40/45 (88.9%) live births and 1/40 (2.5%) infant death; 36 (90%) babies required a permanent pacemaker. The only factor predictive of postnatal death was the presence of CHD (5/9 vs 1/39 or 48.7 [3.6; 1457.7], p < 0.001). Nineteen fetuses (40.5%) with i-AVB received steroids in utero. No difference in outcome was found between the AVB treated in utero versus the no-treatment group in terms of permanent pacemaker placement, postnatal death or development of dilated cardiomyopathy. CONCLUSION: The most important prognostic factor for congenital AVB is the association with CHD. In utero treatment remains questionable.

Contribution to the understanding of the cycle of the protozoan parasite Marteilia refringens.

The paramyxean parasite Marteilia refringens infects several bivalve species including European flat oysters Ostrea edulis and Mediterranean mussels Mytilus galloprovincialis. Sequence polymorphism allowed definition of three parasite types 'M', 'O' and 'C' preferably detected in oysters, mussels and cockles respectively. Transmission of the infection from infected bivalves to copepods Paracartia grani could be experimentally achieved but assays from copepods to bivalves failed. In order to contribute to the elucidation of the M. refringens life cycle, the dynamics of the infection was investigated in O. edulis, M. galloprovincialis and zooplankton over one year in Diana lagoon, Corsica (France). Flat oysters appeared non-infected while mussels were infected part of the year, showing highest prevalence in summertime. The parasite was detected by PCR in zooplankton particularly after the peak of prevalence in mussels. Several zooplanktonic groups including copepods, Cladocera, Appendicularia, Chaetognatha and Polychaeta appeared PCR positive. However, only the copepod species Paracartia latisetosa showed positive signal by in situ hybridization. Small parasite cells were observed in gonadal tissues of female copepods demonstrating for the first time that a copepod species other than P. grani can be infected with M. refringens. Molecular characterization of the parasite infecting mussels and zooplankton allowed the distinguishing of three Marteilia types in the lagoon.

Markers of a recent bocavirus infection in children with Kawasaki disease: "a year prospective study".

BACKGROUND: Retrospective studies and case-reports have suggested the possible role of various viruses in the pathogenesis of the Kawasaki disease. OBJECTIVES: To determine prospectively the incidence of Kawasaki diseases associated with a recent bocavirus infection in the course of a year. STUDY DESIGN: Thirty-two children with Kawasaki disease were enrolled in a 13 months prospective study to assess the frequency of human bocavirus type 1 infections. Seasonal shedding of virus, markers of recent infection such as viraemia, viral load, and serum interferon alpha were analyzed. RESULTS: Three of 32 (9%) children had HBoV-DNA in the serum suggesting a recent infection. HBoV-DNA was detected in naso-pharyngeal aspiration of 7/32 (21.8%) children with Kawasaki Disease and six of them (18%) had an increased viral load. No common respiratory viruses were isolated from the 32 patients with the exception of one adenovirus. The seven bocaviruses were identified during the winter-spring season. In addition, 4 of 7 of Kawasaki disease patients shedding bocavirus had detectable interferon alpha in the blood, indicating a possible active or recent viral infection. CONCLUSIONS: This study shows that a recent bocavirus infection is concomitant with the onset of some cases of Kawasaki disease. Bocavirus may be a cofactor in the pathogenesis of this disease as previously reported for other infectious agents.

Local reference levels and organ doses from pediatric cardiac interventional procedures.

Interventional cardiology (IC) procedures can be responsible for relatively high radiation doses compared to conventional radiology especially for young patients. The aim of this study was to assess current exposure levels in a French reference centre of pediatric IC. Dosimetric data including dose area product (DAP), fluoroscopy time (FT) and number of cine frame (NF) were analysed taking into account patient weight. Doses to the lungs, esophagus, breast and thyroid were evaluated using anthropomorphic phantoms and thermoluminescent dosimeters. Finally, effective doses (E) were calculated using DAP and conversion factors calculated with PCXMC 2.0 software. 801 IC procedures performed between 2010 and 2011 were analysed. Large variations were observed for DAP, FT and NF values for a given procedure and a given weight group. The assessment of organ doses showed high levels of dose to the lungs and esophagus especially in new-born babies. For diagnostic procedures, E varied from 0.3 to 23 mSv with a mean value of 4.8 mSv and for therapeutic procedures, values ranged from 0.1 to 48.4 mSv with a mean value of 7.3 mSv. The highest values were recorded for angioplasty procedures (mean 13 mSv, range 0.6-48.4 mSv). The increasing use of IC in pediatric population stresses the need of setting up reference levels and keeping doses to children as low as possible.

Prenatal diagnosis of isolated total anomalous pulmonary venous connection: a series of 10 cases.

OBJECTIVES: To report on a series of 10 fetuses with prenatally diagnosed isolated total anomalous pulmonary venous connection (TAPVC), focusing on echocardiographic features leading to diagnosis, assess accuracy of prenatal diagnosis and describe postnatal outcome. METHODS: In this review of our experience of prenatal diagnosis of isolated TAPVC, we analyzed retrospectively medical records and fetal echocardiography findings in all cases with prenatal diagnosis of isolated TAPVC delivered between 1 January 2001 and 1 October 2011 at a tertiary referral center, paying special attention to echocardiographic signs that led to referral. RESULTS: During the study period, 95 infants with isolated TAPVC were seen at the center. Initially, expert fetal echocardiography identified 14 fetuses with isolated TAPVC. Prenatal diagnosis was made at a mean gestational age of 31 (range, 25-37) weeks. Ten true-positive cases of TAPVC were confirmed after birth. The remaining four were considered false-positive cases: two had normal heart with left superior vena cava to coronary sinus, one had partial anomalous venous connection and one was lost to follow-up. Of the 85 diagnosed postnatally with TAPVC, only one had been seen prenatally by an expert cardiac sonographer. Echocardiographic signs leading to referral were related to pulmonary venous connection in half of the cases. Other suspected defects which led to referral were ostium prium atrial defect (n = 3), left-right asymmetry (n = 1), abnormal mitral valve (n = 1) and hepatic vascular malformation (n = 1). All infants with TAPVC underwent surgery. There was one postoperative death and nine survivors, with a mean follow-up of 31 (range, 2-104) months. CONCLUSION: Fetal diagnosis of isolated TAPVC is challenging even for experts. Echocardiographic anomalies may appear late in gestation. New tools should be proposed to identify abnormal venous drainage at the screening level.

A gene for Holt-Oram syndrome maps to the distal long arm of chromosome 12.

Holt-Oram syndrome (HOS) is an autosomal dominant condition of unknown origin characterized by congenital septal heart defects with associated malformations of the upper limbs (radial ray). Here, we report on the mapping of a gene causing HOS to the distal long arm of chromosome 12 (12q21-qter) by linkage analysis in nine informative families (Zmax = 6.81 at theta = 0 at the D12S354 locus). Also, multipoint linkage analysis places the HOS gene within the genetic interval between D12S84 and D12S79 (multipoint lod-score in log base 10 = 8.10). The mapping of a gene for HOS is, to our knowledge, the first chromosomal localization of a gene responsible for congenital septal heart defect in human. The characterization of the HOS gene will hopefully shed light on the molecular mechanisms that govern heart septation in the early stages of embryogenesis.

Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.

Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBX5 gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBX5 in heart and limb, consistent with a role in human embryonic development.

Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.

On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34++ CD38-, similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.

A newly discovered class of human hematopoietic cells with SCID-repopulating activity.

The detection of primitive hematopoietic cells based on repopulation of immune-deficient mice is a powerful tool to characterize the human stem-cell compartment. Here, we identify a newly discovered human repopulating cell, distinct from previously identified repopulating cells, that initiates multilineage hematopoiesis in NOD/SCID mice. We call such cells CD34neg-SCID repopulating cells, or CD34neg-SRC. CD34neg-SRC are restricted to a Lin-CD34-CD38- population without detectable surface markers for multiple lineages and CD38 or those previously associated with stem cells (HLA-DR, Thy-1 and CD34). In contrast to CD34+ subfractions, Lin-CD34-CD38- cells have low clonogenicity in short-and long-term in vitro assays. The number of CD34neg-SRC increased in short-term suspension cultures in conditions that did not maintain SRC derived from CD34+ populations, providing independent biological evidence of their distinctiveness. The identification of this newly discovered cell demonstrates complexity of the organization of the human stem-cell compartment and has important implications for clinical applications involving stem-cell transplantation.

Multifactorial origin of pulmonary hypertension in a child with congenital heart disease, Down syndrome, and BMPR-2 mutation.

A late preterm infant had pulmonary hypertension caused by a variety of mechanisms leading to complex management. This child had complete atrioventricular septal defect associated with mild left ventricular hypoplasia and Down syndrome diagnosed prenatally. The mother had been treated by antiretroviral HIV treatment during pregnancy. Aortic coarctation was diagnosed and rapidly repaired. After surgery, he required noninvasive ventilation for persisting elevated PCO2. Pulmonary CT scan showed normal bronchial tree, lung parenchymal abnormalities with mosaic aspect and hyperlucent zones, and indirect signs of lung hypoplasia with peripheral microbubbles. During follow-up, severe pulmonary hypertension was diagnosed on echocardiography without recoarctation, significant intracardiac shunting or diastolic dysfunction. The patient died after four months unable to be weaned from noninvasive ventilation. Post mortem lung biopsy showed abnormally muscularized arterioles with intimal fibrosis and pulmonary immaturity. Gentetic screening identified a BMPR-2 mutation. This patient illustrates the multifactorial origin of pulmonary hypertension in the neonatal period. The respective contribution of left-to-right shunt, post-capillary obstruction, and abnormally elevated pulmonary vascular resistances led to perform right heart catheterization to exclude excessive shunting and restrictive physiology of the left heart. Subjects with Down syndrome are also highly susceptible to decreased lung vascular and alveolar growth, which may increase the risk for pulmonary hypertension and lung hypoplasia. This case highlights two issues. The first one is that right heart catheterization should be discussed in neonates with unexplained pulmonary hypertension and the second is to extend indications of genetic testing for pulmonary hypertension genes in neonates who have unusual course of neonatal pulmonary hypertension, particularly in the setting of associated congenital heart disease (CHD).

Respiratory morbidity in children with congenital heart disease.

OBJECTIVE: To evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology. DESIGN AND SETTING: Clinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort. PATIENTS: Children were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113). RESULTS: Current wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values. CONCLUSION: Lower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development.

[Prenatal path of care following the diagnosis of a malformation for which a novel prenatal therapy is available]. / Parcours prénatal devant une malformation pour laquelle un traitement in utero émergent est disponible.

OBJECTIVES: Fetal therapy is part of the available care offer for several severe malformations. The place of these emergent prenatal interventions in the prenatal path of care is poorly known. The objective of this study is to describe the decision-making process of patients facing the option of an emergent in utero intervention. METHODS: We have conducted a retrospective monocentric descriptive study in the department of maternal-fetal medicine of Necker Hospital. We collected data regarding eligibility or not for fetal surgery and the pregnancy outcomes of patients referred for myelomeningocele, diaphragmatic hernia, aortic stenosis and low obstructive uropathies. RESULTS: All indications combined, 70% of patients opted for fetal surgery. This rate was lower in the case of myelomeningocele with 21% consent, than in the other pathologies: 69% for diaphragmatic hernias, 90% for aortic stenoses and 76% for uropathy. When fetal intervention was declined, the vast majority of patients opted for termination of pregnancy: 86%. In 14% of the considering fetal surgery, the patient was referred too far. CONCLUSION: The acceptance rate for fetal surgeries depends on condition. It offers an additional option and is an alternative for couples for which termination of pregnancy (TOP) is not an option. Timely referral to an expert center allows to discuss the place of a fetal intervention and not to deprive couples of this possibility.

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.