Selective Sparing Research Articles

Surgical Subinguinal Approach to Varicocele Combined With Antegrade Intraoperative Sclerosis of Venous Vessels

Varicocele is treated by different surgical techniques, none of which is yet acknowledged as the "gold standard." Some of these techniques, especially microsurgical techniques, are very time consuming and thus expensive, and the treatment of varicocele still causes some complications and recurrences. Marmar and Kim's technique presents some indisputable advantages: it allows the preservation of the arteries and seems to offer the highest percentage of success and lowest number of complications. The authors modified and simplified the microsurgical technique of Marmar and Kim, using a subinguinal approach with intraoperative antegrade sclerotherapy of dilated veins. After the cord has been clamped, 1.5 to 3 mL of 3% aetoxisclerol mixed with 0.5 mL of air is injected. Commonly, minor complications can occur. The most common complication is transient penile lymphangitis, the cause of which is unclear. As the procedure allows selective sparing of the lymphatic vessels, it avoids hydrocele due to the performed procedure.

Somatostatin Receptor 1 and 5 Double Knockout Mice Mimic Neurochemical Changes of Huntington's Disease Transgenic Mice

BackgroundSelective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD). However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST) positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5).Methods and FindingsTo delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2). Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32) and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5−/− and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.ConclusionsThis is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

Factors contributing to failure of neuromuscular transmission in myasthenia gravis and the special case of the extraocular muscles

Acetylcholine receptors (AchRs) and Na(+) channels (NaChs) are concentrated on neuromuscular junction (NMJ) postsynaptic folds; both are depleted in myasthenia gravis (MG), reducing the safety factor (SF) for neuromuscular transmission, especially in extraocular muscles (EOM). Studies of human myasthenic nerve-muscle preparations indicate that loss of endplate AChRs accounts for 59%, and NaChs for 40%, of SF reduction. Rodent models of MG indicate that NaChs and AChRs losses are due to complement-mediated destruction of postsynaptic folding. Saccades in MG show stereotyped, conjugate initial components, similar to normal but different from early disconjugacy with ocular nerve palsies. Loss of AChRs, NaChs, and postsynaptic folding all contribute to SF reduction in MG. EOM seem more susceptible to MG because of poor postsynaptic folding, lower baseline SF, and lower levels of intrinsic complement inhibitors. Initial conjugacy of saccades in MG reflects selective sparing of neuromuscular transmission of fast, pale global fibers, which have better developed postsynaptic folding.

When two and too don’t go together: A selective phonological deficit sparing number words

We report the case of an Italian speaker (GBC) with classical Wernicke’s aphasia syndrome following a vascular lesion in the left posterior middle temporal region. GBC exhibited a selective phonological deficit in spoken language production (repetition and reading) which affected all word classes irrespective of grammatical class, frequency, and length. GBC’s production of number words, in contrast, was error free. The specific pattern of phonological errors on non-number words allows us to attribute the locus of impairment at the level of phonological form retrieval of a correctly selected lexical entry. These data support the claim that number words are represented and processed differently from other word categories in language production.

Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder

Recent functional connectivity magnetic resonance imaging and diffusion tensor imaging (DTI) studies have suggested atypical functional connectivity and reduced integrity of long-distance white matter fibers in autism spectrum disorder (ASD). However, evidence for short-distance white matter fibers is still limited, despite some speculation of potential sparing of local connectivity in ASD. Short-distance U-fibers are an important component of neural networks and are thought to play a crucial role in cognitive function. In the present study, we applied tract-based spatial statistics to derive short- and long-distance white matter tracts in frontal, parietal, and temporal lobes in both hemispheres. DTI data were acquired from 26 children with ASD and 24 typically developing (TD) children. A mean fractional anisotropy (FA) image was created and thinned to represent centers of all common tracts. Evidence of compromised short-distance tracts for the ASD group was found in frontal lobe (reduced FA, increased mean diffusivity [MD] and radial diffusivity) as well as in temporal and parietal lobes (increased MD and radial diffusivity). Significant positive correlations between age and FA and negative correlations between age and MD and radial diffusivity were also found for short-distance tracts in each lobe in the TD, but not the ASD group. These results suggest white matter compromise in short-distance tracts in ASD. Absence of typical age-related correlations with DTI indices may reflect altered maturation of short-distance tracts in ASD. Our results are inconsistent with a notion of selective sparing of short-distance connectivity in ASD.

Naming with proper names: the left temporal pole theory.

Existing empirical data on proper names processing are critically reviewed in trying to understand which tasks may involve the left temporal pole, which proper name related functions are supported by this structure and eventually offer some speculations about why these functions might have developed in this location in the course of human evolution. While clinical group studies support the idea that proper name processing takes place in the left temporal pole, single case studies of selective proper name anomia or sparing, as well as neuroimaging studies, suggest the involvement of a larger neural network. Within this network, an important role may be played by the ventro-medial prefrontal cortex, including areas critical in social interaction. The differentiation in the brain of proper name processing from common names processing could in part be due to social pressure, favouring a neural system able to more efficiently and unambiguously sustain designating categories or designating individual entities. The activation of the left temporal pole in proper name processing is shown to increase with age. Longer social interaction may thus contribute to convey proper names processing toward areas closer to those supporting social cognition.

The wide window of face detection

Faces are detected more rapidly than other objects in visual scenes and search arrays, but the cause for this face advantage has been contested. In the present study, we found that under conditions of spatial uncertainty, faces were easier to detect than control targets (dog faces, clocks and cars) even in the absence of surrounding stimuli, making an explanation based only on low-level differences unlikely. This advantage improved with eccentricity in the visual field, enabling face detection in wider visual windows, and pointing to selective sparing of face detection at greater eccentricities. This face advantage might be due to perceptual factors favoring face detection. In addition, the relative face advantage is greater under flanked than non-flanked conditions, suggesting an additional, possibly attention-related benefit enabling face detection in groups of distracters.

Effect of sex and estrogen therapy on the aging brain

It is still a matter of debate whether estrogen can have a protective effect on brain integrity and against age- and Alzheimer-related assaults. Evidence points toward selective sparing of gray matter (GM) in postmenopausal women using hormone therapy. In the current study, the effect of sex and estrogen therapy (ET) exposure on GM density using voxel-based morphometry was assessed. High-resolution structural magnetic resonance imaging scans of 46 healthy participants were analyzed using voxel-based morphometry. A total of 15 men and 31 healthy postmenopausal women were included: 15 ET-naive women (never users) and 16 current ET users with an average duration of use of 11 years. Sex differences were found in fronto-temporo-parietal areas, with postmenopausal women having greater GM concentration in the medial prefrontal cortex, temporal cortices, angular gyrus, and precuneus, whereas the men had greater GM density in the superior frontal, inferior temporal gyri, and inferior parietal lobules. ET users compared with never users had greater GM density in the superior frontal gyrus and less GM density in the posterior part of the hippocampus and parahippocampal gyrus, posterior cingulate, and angular gyri. In the group of ET users, a negative association was found between duration of ET use and posterior hippocampus and parahippocampal GM density, whereas a positive association was found in the hypothalamus, striatum, precunei, and inferior parietal lobules. These results point toward a potential regional- and duration-dependent estrogen exposure effect on cerebral areas known to be involved in age-related cognitive functions and Alzheimer and Parkinson diseases.

FP34-WE-01 Evidence for selective sparing of fast extraocular muscle fibers in ocular myasthenia gravis

FP34-WE-01 Evidence for selective sparing of fast extraocular muscle fibers in ocular myasthenia gravis

Intensity modulated radiotherapy (IMRT) in the treatment of children and Adolescents - a single institution's experience and a review of the literature

BackgroundWhile IMRT is widely used in treating complex oncological cases in adults, it is not commonly used in pediatric radiation oncology for a variety of reasons. This report evaluates our 9 year experience using stereotactic-guided, inverse planned intensity-modulated radiotherapy (IMRT) in children and adolescents in the context of the current literature.MethodsBetween 1999 and 2008 thirty-one children and adolescents with a mean age of 14.2 years (1.5 - 20.5) were treated with IMRT in our department. This heterogeneous group of patients consisted of 20 different tumor entities, with Ewing's sarcoma being the largest (5 patients), followed by juvenile nasopharyngeal fibroma, esthesioneuroblastoma and rhabdomyosarcoma (3 patients each). In addition a review of the available literature reporting on technology, quality, toxicity, outcome and concerns of IMRT was performed.ResultsWith IMRT individualized dose distributions and excellent sparing of organs at risk were obtained in the most challenging cases. This was achieved at the cost of an increased volume of normal tissue receiving low radiation doses. Local control was achieved in 21 patients. 5 patients died due to progressive distant metastases. No severe acute or chronic toxicity was observed.ConclusionIMRT in the treatment of children and adolescents is feasible and was applied safely within the last 9 years at our institution. Several reports in literature show the excellent possibilities of IMRT in selective sparing of organs at risk and achieving local control. In selected cases the quality of IMRT plans increases the therapeutic ratio and outweighs the risk of potentially increased rates of secondary malignancies by the augmented low dose exposure.

Recent Advances in Breast Cancer-Related Lymphedema of the Arm: Lymphatic Pump Failure and Predisposing Factors

Axillary surgery for breast cancer may be followed, months to years later, by chronic arm lymphedema. A simple 'stopcock' mechanism (reduced lymph drainage from the entire limb through surviving lymphatics) does not explain many clinical aspects, including the delayed onset and selective sparing of some regions, e.g., hand. Quantitative lymphoscintigraphy reveals that lymph drainage is slowed in the subcutis, where most of the edema lies, and in the subfascial muscle compartment, which normally has much higher lymph flows than the subcutis. Although the muscle does not swell significantly, the impaired muscle drainage correlates with the severity of arm swelling, indicating a likely key role for muscle lymphatic function. A new method, lymphatic congestion lymphoscintigraphy, showed that the edema is associated with a reduced contractility of the arm lymphatics; the weaker the active lymphatic pump, the greater the swelling. Delayed lymphatic pump failure may result from chronic raised afterload, as in hypertensive cardiac failure, and may account for the delayed onset of swelling. A further novel finding is that lymph flow is raised in both the subcutis and muscle of both arms in postsurgical breast patients who later developed breast cancer-related lymphedema (BCRL), compared with patients who did not develop BCRL. This new observation indicates a predisposition to BCRL in some women. Further evidence for predisposing abnormalities is the finding of lymphatic abnormalities in the contralateral (nonswollen) arm in women with established BCRL. Such predisposing factors could explain why some women develop BCRL after sentinel node biopsy, whereas others do not after clearance surgery. Future research must focus on prospective observations made from before surgery until BCRL develops.

Reversed concreteness effect for nouns in a subject with semantic dementia

Selective sparing of abstract relative to concrete words has been documented only exceptionally in aphasia, following bilateral temporal damage. In this paper we present a new case with sparing of abstract word processing and impairment of concrete words due to selective atrophy of the left anterior temporal regions.In our subject, the reversal of the concreteness effect was restricted to nouns. Performance on nouns was not homogeneous. Proper names (people and landmarks) were very severely damaged. Among common names, living entities were selectively impaired in comparison to non-living entities. Category-specific damage for living beings resulted from widespread loss of conceptual information, and perceptual information was less impaired than associative knowledge. This observation challenges theories explaining the reversal of concreteness effect with a selective loss of perceptual information. Also the alternative account, namely a different representational architecture for abstract as opposed to concrete terms, with an advantage for concrete words accruing from an impairment of categorical information, fails to account for the data.Most subjects showing preserved knowledge of abstract words, relative to concrete words, suffer from diseases affecting anterior temporal regions (semantic dementia, herpes encephalitis), and frequently present with greater, or unilateral involvement of the left hemisphere. Our case converges with similar previous reports and with some neuroimaging studies in suggesting that the right temporal lobe and probably the left inferior prefrontal gyrus play a crucial role in the representation of abstract concepts.

Evidence for relative cortical sparing in benign multiple sclerosis: a longitudinal magnetic resonance imaging study

Background Using double inversion recovery (DIR) MRI, cortical lesions can be seen in the brain of patients with multiple sclerosis (MS). The burden of such lesions seems to be well correlated with the severity of MS-related disability. Objective To investigate whether the extent of cortical damage in patients with benign MS (BMS) might contribute to explain their favorable clinical status. Methods Forty-eight patients with BMS (Expanded Disability Status Scale [EDSS] score ≤3.0 and disease duration ≥15 years) and 96 patients with non-disabling, early relapsing–remitting (RR) MS (EDSS score ≤3.0 and disease duration ≤5 years) were studied. Brain MRI, including a DIR and a fluid-attenuated inversion recovery (FLAIR) sequence, was acquired at baseline and after 12 months. On DIR images, intracortical (ICL) and cortical-subcortical lesions (CSL) were identified and their number and volume calculated. Total white matter (WM) lesion volume was quantified on FLAIR images. Results Compared with early RRMS, patients with BMS had lower number of ICL at both study time points (P ≤ 0.001 for both comparisons). At one-year follow-up, a significant increase of ICL and CSL number and total volume was observed only in early patients with RRMS. The number and volume of cortical lesions was not correlated with WM lesion volume. Total ICL number at baseline, total cortical lesion volume at baseline, and total cortical lesion volume change were independent predictors of MS phenotype. Conclusion In patients with BMS, the selective sparing of the cortex from disease-related focal pathology might be one of the factors associated to their favorable clinical status, independently of the (possible) accrual of WM lesions.

Somatostatin in Medium-Sized Aspiny Interneurons of Striatum is Responsible for Their Preservation in Quinolinic Acid and N-Methyl-d-Asparate-Induced Neurotoxicity

Somatostatin (SST) is a multifunctional peptide and involves in several neurodegenerative diseases. N-Methyl-D-asparate (NMDA) receptor agonist quinolinic acid (QUIN)-induced neurotoxicity mimics an experimental model of Huntington's disease that is characterized by the selective preservation of medium-sized aspiny interneurons and degeneration of medium-sized spiny projection neurons in striatum. In QUIN- and NMDA-induced neurotoxicity, increased expression of SST and messenger RNA levels along with SST release in culture medium is generally observed. However, the molecular mechanisms and the functional consequences of increased SST are still obscure. In the present study, the role of SST was determined using immunoneutralization and immunoblockade of SST in cultured striatal neurons upon QUIN- and NMDA-induced neurotoxicity. The immunoblockade of SST with antisense oligonucleotides and immunoabsorption of released SST with specific antibodies potentiate QUIN- and NMDA-induced neuronal cell death. NADPH-diaphorase positive neurons that are selectively spared in several processes of neurodegeneration result in severe damage upon immunoblockade or immunoabsorption of SST. In addition, exogenous SST along with QUIN and NMDA provides selective preservation of projection neurons, which are selectively susceptible in excitotoxicity. Neuroprotective effect of SST is completely blocked by pertussis toxins, suggesting the role of somatostatin receptors. Taken together, these results provide first evidence that the presence of SST is a unique feature for the selective sparing of medium sized aspiny interneurons in excitotoxicity.

Ocular myasthenia revisited: Insights from pseudo-internuclear ophthalmoplegia

Ocular myasthenia can mimic central disorders of eye movements. We compared horizontal saccades in two patients with myasthenia gravis who presented as pseudo-internuclear ophthalmoplegia (pseudo-INO), two patients with true INO due to multiple sclerosis (MS), and five healthy subjects. In myasthenics, peak velocity of horizontal saccades was similar to, or greater than, controls; in MS patients, adducting saccades were slower than controls. Differences between the peak velocity of abducting and adducting eyes for each saccade were similar to controls for myasthenic pseudo-INO, but greater than controls for true INO. Using the technique of phase-plane analysis, in which eye velocity is plotted against eye position, we found that initial components of abducting and adducting saccades in the myasthenics were as conjugate as controls, even though later components of myasthenic saccades were highly and variably disjunctive. Conversely, phase planes of saccades in true INO showed disjunctive early components of abducting and adducting saccades. Two hypotheses have been offered to account for preservation of fast saccades despite reduced range of eye movements in ocular myasthenia. The first is intrasaccadic neuromuscular fatigue, which is variable over time. Our finding that initial components of saccades were consistently conjugate in the myasthenics gives support to a second hypothesis: selective sparing of pale global fibers, which are important for generating highspeed eye movements, and which are unique amongst extraocular fibers in possessing well developed synaptic folding.

Deafness for the meanings of number words

We describe the performance of an aphasic individual who showed a selective impairment affecting his comprehension of auditorily presented number words and not other word categories. His difficulty in number word comprehension was restricted to the auditory modality, given that with visual stimuli (written words, Arabic numerals and pictures) his comprehension of number and non-number words was intact. While there have been previous reports of selective difficulty or sparing of number words at the semantic and post-semantic levels, this is the first reported case of a pre-semantic deficit that is specific to the category of number words. This constitutes evidence that lexical semantic distinctions are respected by modality-specific neural mechanisms responsible for providing access to the meanings of words.

Superficial siderosis of the CNS: selective central myelin vulnerability and peripheral myelin sparing demonstrated by MRI

Superficial siderosis of the CNS: selective central myelin vulnerability and peripheral myelin sparing demonstrated by MRI

Impaired spatial working memory but spared spatial reference memory following functional loss of NMDA receptors in the dentate gyrus.

Novel spatially restricted genetic manipulations can be used to assess contributions made by synaptic plasticity to learning and memory, not just selectively within the hippocampus, but even within specific hippocampal subfields. Here we generated genetically modified mice (NR1ΔDG mice) exhibiting complete loss of the NR1 subunit of the N-methyl-d-aspartate receptor specifically in the granule cells of the dentate gyrus. There was no evidence of any reduction in NR1 subunit levels in any of the other hippocampal subfields, or elsewhere in the brain. NR1ΔDG mice displayed severely impaired long-term potentiation (LTP) in both medial and lateral perforant path inputs to the dentate gyrus, whereas LTP was unchanged in CA3-to-CA1 cell synapses in hippocampal slices. Behavioural assessment of NR1ΔDG mice revealed a spatial working memory impairment on a three-from-six radial arm maze task despite normal hippocampus-dependent spatial reference memory acquisition and performance of the same task. This behavioural phenotype resembles that of NR1ΔCA3 mice but differs from that of NR1ΔCA1 mice which do show a spatial reference memory deficit, consistent with the idea of subfield-specific contributions to hippocampal information processing. Furthermore, this pattern of selective functional loss and sparing is the same as previously observed with the global GluR-A l-α-amino-3-hydroxy-5-methyl-4-isoxazelopropionate receptor subunit knockout, a mutation which blocks the expression of hippocampal LTP. The present results show that dissociations between spatial working memory and spatial reference memory can be induced by disrupting synaptic plasticity specifically and exclusively within the dentate gyrus subfield of the hippocampal formation.

β‐Amyloid increases somatostatin expression in cultured cortical neurons

In beta-amyloid (Abeta)-induced neurotoxicity, activation of the NMDA receptor, increased Ca2+ and oxidative stress are intimately associated with neuronal cell death as normally seen in NMDA-induced neurotoxicity. We have recently shown selective sparing of somatostatin (SST)-positive neurons and increased SST expression in NMDA agonist-induced neurotoxicity. Accordingly, the present study was undertaken to determine the effect of Abeta25-35-induced neurotoxicity on the expression of SST in cultured cortical neurons. Cultured cortical cells were exposed to Abeta25-35 and processed to determine the cellular content and release of SST into medium by radioimmunoassay and SST mRNA by RT-PCR. Abeta25-35 induces neuronal cell death in a concentration- and time-dependent fashion, increases SST mRNA synthesis and induces an augmentation in the cellular content of SST. No significant changes were seen on SST release at any concentration of Abeta25-35 after 24 h of treatment. However, Abeta25-35 induces a significant increase of SST release into medium only after 12 h in comparison with other time points. Most significantly, SST-positive neurons are selectively spared in the presence of a lower concentration of Abeta25-35, whereas, in the presence of higher concentrations of Abeta25-35 for extended time periods, SST-positive neurons decrease gradually. Furthermore, Abeta25-35 induces apoptosis at lower concentrations (5 and 10 micromol/L) and necrosis at higher concentrations (20 and 40 micromol/L). Consistent with the increased accumulation of SST, these data suggest that Abeta25-35 impairs cell membrane permeability. Selective sparing of SST-positive neurons at lower concentrations of Abeta25-35 at early time points directly correlates with the pathophysiology of Alzheimer's disease.

Acute Myeloid Leukemia Remission Bone Marrow Reveals the Presence of Malignant and Normal Side Population (SP) Stem Cells Whose Frequencies and Ratios Predict Clinical Outcome.

A high relapse rate in AML suggests that present therapies are ineffective in eliminating leukemic stem cells. These may be present in the side population (SP) cells, which are able initiate leukemia in NOD/SCID mice. LSC detection may offer opportunities for detection of stem cells under conditions of minimal residual disease (MRD). Separately (Moshaver, this meeting) we show that leukemia associated immunophenotypes (LAP; used for MRD detection, Feller, Leukemia 18:1380, 2004) and CD34+CD38- stem cell marker C-type Lectin-like molecule-1 (CLL-1, van Rhenen, Blood 106: 6a, 2005), and Il-3 receptor α-chain CD123, are able to discriminate between normal and leukemic SP stem cells at diagnosis. In addition, LAP marker and CLL-1 expression, but not CD123 expression, on SP cells in control bone marrows (n=12) was lacking. SP cells could be detected in 13/17 diagnosis AML patients. The contribution of the AML SP to total SP was calculated based on expression of above-mentioned AML markers and checked with FISH analysis. We further use “AML SP frequency” (AML SP as % of WBC) and “AML SP fraction” (AML SP as fraction of total SP). We obtained 12 follow-up samples of 6 of these patients. At diagnosis median AML SP frequency was 0.015 and median AML SP fraction was 0.7. At follow-up, median total SP frequency was 0.01% (0.0007%–2.0 %). AML SP frequency herein was median 0.004% (<0.00001 – 1.05). AML SP frequency detection was compared with MRD detection method, known to predict prognosis (Feller, 2004). In 5/6 patients with low AML SP frequencies (< 0.004%) MRD was undetectable (≤0.01%). In 4/6 patients with high frequencies, MRD>0.01% was found. 3/6 patients showed a remarkable phenomenon: AML SP frequency was relatively high (0.006%, 0.007% and 0.014%, respectively) with apparently non-matching, relatively low MRD frequencies (0.02%, 0.02% and 0.01%, resp.), but with a drastic increase of MRD frequency at the next sampling time point (to 0.17%, 0.11% and 0.21%, resp). Such increases as well as the absolute percentages (>0.1%) inevitably lead to relapse (Feller 2004), which at present short follow up time already occurred for one patient. In addition, AML SP fraction was compared with MRD: 5/5 with low AML SP fraction (<0.21) had no detectable MRD (MRD≤0.01%). For high AML SP fraction (≥0.21) 4/6 had MRD>0.01%. AML SP fraction identified the same 3 special patients as did AML SP frequency: the AML SP fraction was high (0.33, 0.64 and 1.0, resp.) with the low MRD frequencies that subsequently strongly increased. Both stem cell parameters thus add additional prognostic value to MRD assessment. In conclusion, AML and normal stem cells can be detected with great specificity in AML remission bone marrow using LAP markers and CLL-1, that specifically stain AML SP stem cells and not normal SP stem cells. Additional predictive power for forthcoming relapses comes from the selective sparing of AML SP stem cells after therapy compared to both the more mature AML cells and the normal stem cells. The introduction of such stem cell parameters may thus contribute to MRD based risk stratification during treatment, offer guidelines for future clinical intervention time points, while studying cellular characteristics of both AML and normal stem cells may allow to design stem cell directed therapies that are effective for eradication of AML stem cells with minimal toxicity towards normal stem cells.