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Presents abstracts on the results of two research studies involving kidney diseases. Renal growth in children with severe vesicouretal reflux who undergo either medical or surgical treatment; Identification of a type of chronic renal failure-causing human adolescent nephronophthisis.

DNA sequence enrichment from complex genomic samples using microarrays enables targeted next-generation sequencing (NGS). In this study, we combined 454 shotgun pyrosequencing with long oligonucleotide sequence capture arrays. We demonstrate the detection of mutations including point mutations, deletions and insertions in a cohort of 22 patients presenting with acute leukemias and myeloid neoplasms. Importantly, this one-step methodological procedure also allowed the detection of balanced chromosomal aberrations, including translocations and inversions. Moreover, the genomic representation of only one of the partner genes of a chimeric fusion on the capture platform also permitted identification of the novel fusion partner genes. Using acute myeloid leukemias harboring RUNX1 abnormalities as a model system, three novel chromosomal fusion sequences and KCNMA1 as a novel RUNX1 fusion partner gene were detected. This assay has the strong potential to become an important method for the comprehensive genetic characterization of particular leukemias and other malignancies harboring complex genomes. [ABSTRACT FROM AUTHOR]

A letter to the editor related to the deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations.

Fluctuations in estrogen and progesterone during the menstrual cycle can cause changes in body systems other than the reproductive system. We conducted several studies to determine a possible correlation between phases of the menstrual cycle and specific skin properties. Healthy Caucasian women (ages 21–48), who had a typical 26–29 day menstrual cycle, participated in the studies. Measurements of skin barrier strength, dryness, response to lactic acid stinging, skin surface lipids, and microflora were obtained every week for 2 to 3 months. Ultraviolet B (UV-B) susceptibility in terms of minimal erythemal dose was also studied. The skin barrier was the weakest between days 22 and 26 of the cycle. Elevated neuronal response (lactic acid sting) was not observed to vary much with the cycle. Skin was driest between day 1 and day 6, while skin surface lipid secretion appeared to be highest on days 16–20 of the hormonal cycle. The highest microbial count was around days 16–22, and there was a high UV-B susceptibility between days 20 and 28 of the menstrual cycle. [ABSTRACT FROM AUTHOR]

A letter to the editor related to mutation analysis for myelodysplastic syndromes is presented.

A letter to the editor is presented in the response of the article "Gene expression profiling in AML with normal karyotype can predict mutations for molecular markers and allows novel insights into perturbed biological pathways," in April 29, 2010 issue.

A letter to the editor is presented related to abnormal bone marrow in patients with Acute myeloid leukemia.

A letter to the editor is presented discussing acute myeloid leukemia with limited differentiation and NPM1 type A mutation.

Balanced chromosomal rearrangements define distinct entities in acute myeloid leukemia (AML). Here, we present 13 AML cases with t(8;16)(p11;p13) with observed low incidence (13/6124 patients), but more frequent presentation in therapy-related AML than in de novo AML (7/438 versus 6/5686, P=0.00001). Prognosis was poor with median overall survival of 4.7 months. Cytomorphology was characterized by parallel positive myeloperoxidase and non-specific esterase staining, therefore, French-American-British (FAB)-classification was impossible and origin of the AML with t(8;16) from an early stem cell with myeloid and monoblastic potential is hypothesized. Erythrophagocytosis was observed in 7/13 cases. Using gene expression profiling on 407 cases, patients with t(8;16) were compared to AML FAB subtypes with normal karyotype. Principal component analyses demonstrated that AML with t(8;16) were distinct from FAB subtypes M1, M4, M5a/b. When further compared to AML showing balanced rearrangements, that is, current WHO categories t(15;17), t(8;21), inv(16) and t(11q23)/MLL, AML with t(8;16) cases were clustered close to t(11q23)/MLL sharing commonly expressed genes. Subsequently, a pairwise comparison discriminated AML with t(8;16) from AML with t(11q23)/MLL, thus defining a highly unique signature for AML with t(8;16). In conclusion, AML with t(8;16) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features and is a specific subtype of AML. [ABSTRACT FROM AUTHOR]

Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by real-time PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.Bone Marrow Transplantation (2008) 42, 145–157; doi:10.1038/bmt.2008.185; published online 30 June 2008 [ABSTRACT FROM AUTHOR]

This article discusses a case study where a patient with primary myelofibrosis acquired acute myeloid leukemia (AML) following a possible mutation in the cytoplasmic nucleophosmin protein (NPM). This development was accompanies by a low white blood cell count and anaemia. The question of whether or note the AML was caused by genetic mutations accompanying the primary myelofibrosis is explored.

The FIP1L1-PDGFRA fusion gene has been described in patients with eosinophilia-associated myeloproliferative disorders (Eos-MPD). Here, we report on seven FIP1L1-PDGFRA-positive patients who presented with acute myeloid leukemia (AML, n=5) or lymphoblastic T-cell non-Hodgkin-lymphoma (n=2) in conjunction with AML or Eos-MPD. All patients were male, the median age was 58 years (range, 40–66). AML patients were negative for common mutations of FLT3, NRAS, NPM1, KIT, MLL and JAK2; one patient revealed a splice mutation of RUNX1 exon 7. Patients were treated with imatinib (100 mg, n=5; 400 mg, n=2) either as monotherapy (n=2), as maintenance treatment after intensive chemotherapy (n=3) or in overt relapse 43 and 72 months, respectively, after primary diagnosis and treatment of FIP1L1-PDGFRA-positive disease (n=2). All patients are alive, disease-free and in complete hematologic and complete molecular remission after a median time of 20 months (range, 9–36) on imatinib. The median time to achievement of complete molecular remission was 6 months (range, 1–14). We conclude that all eosinophilia-associated hematological malignancies should be screened for the presence of the FIP1L1-PDGFRA fusion gene as they are excellent candidates for treatment with tyrosine kinase inhibitors even if they present with an aggressive phenotype such as AML.Leukemia (2007) 21, 1183–1188. doi:10.1038/sj.leu.2404662; published online 22 March 2007 [ABSTRACT FROM AUTHOR]

The outcome of 45 AML1-ETO-positive acute myeloid leukemia (AML) patients was analyzed with special emphasis on the quality of molecular response to therapy. Patients received double induction therapy, either 6-thioguanine, cytarabine, and daunorubicin (TAD9)/high-dose cytosine arabinoside plus mitoxantrone (HAM) or HAM/HAM, followed by consolidation therapy (TAD9) according to the AML-Cooperative group 92 trial (AMLCG92) and AML-Cooperative group 99 trial (AMLCG99). All cases underwent cytomorphological, cytogenetical and molecular genetic analyses. AML1-ETO transcript levels were quantitatively assessed at diagnosis and during follow-up by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The median reduction of initial AML1-ETO expression level was 4 log (range 0–5) after both induction and consolidation therapies. The quality of molecular response after induction as well as consolidation therapies had significant impact on the cumulative incidence of relapse (P=0.021 and P=0.001, respectively), event free survival (EFS: P=0.001 and P=0.001, respectively) and overall survival (OS: P=0.013 and P=0.014, respectively). HAM/HAM improved the molecular response to induction therapy (P=0.042) but after consolidation, no differences in molecular response were detectable between TAD9/HAM and HAM/HAM. Patient- or disease-related factors had no impact on the molecular response to induction or consolidation therapy. The current study demonstrates that quantification of AML1-ETO transcript levels is a powerful tool for prediction of prognosis that is independent of pretreatment risk factors, and may be helpful for directing therapeutic decisions in the future.Leukemia (2007) 21, 1177–1182. doi:10.1038/sj.leu.2404659; published online 22 March 2007 [ABSTRACT FROM AUTHOR]

Chromosomal rearrangements of the human MLL gene are a hallmark for aggressive (high-risk) pediatric, adult and therapy-associated acute leukemias. These patients need to be identified in order to subject these patients to appropriate therapy regimen. A recently developed long-distance inverse PCR method was applied to genomic DNA isolated from individual acute leukemia patients in order to identify chromosomal rearrangements of the human MLL gene. We present data of the molecular characterization of 414 samples obtained from 272 pediatric and 142 adult leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified. The combined data of our study and published data revealed a total of 87 different MLL rearrangements of which 51 TPGs are now characterized at the molecular level. Interestingly, the four most frequently found TPGs (AF4, AF9, ENL and AF10) encode nuclear proteins that are part of a protein network involved in histone H3K79 methylation. Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected. [ABSTRACT FROM AUTHOR]

Abstract: Genetic and molecular techniques have provided increasing insights into the biology of acute myeloid leukemia (AML). These investigations showed that AML is not a homogeneous disease but a heterogeneous group of biologically different subentities. These subentities are currently primarily defined by cytogenetics by which three main subgroups can be discriminated: AML with balanced translocations, AML with unbalanced aberrations and AML without cytogenetically detectable aberrations. Within the latter group molecular alterations are identified in more than half of cases such as NPM mutations, FLT3 mutations, MLL duplications and mutations of CEBP-α. The clinical meaning of these findings is illustrated by substantial differences in response to therapy and long-term outcome. As demonstrated by the recent multicenter trial of the German AML Cooperative Group (AMLCG) and other studies intensification of induction therapy may improve the results in distinct subtypes but fails to do so in others. Therefore, new strategies need to be explored which incorporate the knowledge about the biology of AML to develop biology adapted treatment strategies. This process has just begun and is predominantly determined by the availability of new agents and their evaluation in clinical phase I and II studies. A variety of targets are currently explored and some trials have yielded promising results already. The step towards a biology adapted treatment of AML is long and requires the combined efforts of researchers, clinicians and the pharmaceutical industry. The first steps towards this goal have been taken and give rise to the hope for more effective and more specific therapies of AML. [Copyright &y& Elsevier]

In search for general PCR targets for minimal residual disease (MRD) studies in acute myeloid leukemia (AML), Wilms' tumor gene 1 (WT1) expression was assessed by real-time RT-PCR relative to the control gene ABL in 569 archived samples of AML patients (pts). Pts were analyzed at diagnosis (n=116) and during follow-up (n=105, median 4 times, range 2–17). Median follow-up time was 258 days (range 16–1578 days). In 66 pts, the WT1 expression was analyzed in comparison to a second PCR marker or to multiparameter flow cytometry. Quantitative WT1 levels correlated to the clinical course or a second marker in 83–96% of the cases. Prognostic significance of WT1 levels was analyzed at diagnosis and three intervals: (1) days 16–60, (2) days 61–120, and (3) days 121–180 after start of chemotherapy. Higher levels of WT1 expression were associated with shorter overall survival (OS) and event-free survival (EFS) within intervals 2 and 3 but not at diagnosis or interval 1. In addition, within these intervals, WT1/ABL levels 0.4% were associated with improved OS and EFS. An increase of WT1 levels was detected in 16/44 cases, which subsequently relapsed within a median of 38 days (range 8–180 days). In conclusion, quantification of WT1 may be used for MRD studies and for prognostification in AML.Leukemia (2005) 19, 1416–1423. doi:10.1038/sj.leu.2403809; published online 26 May 2005 [ABSTRACT FROM AUTHOR]

We performed microarray analyses in AML with trisomies 8 (n=12), 11 (n=7), 13 (n=7), monosomy 7 (n=9), and deletion 5q (n=7) as sole changes to investigate whether genomic gains and losses translate into altered expression levels of genes located in the affected chromosomal regions. Controls were 104 AML with normal karyotype. In subgroups with trisomy, the median expression of genes located on gained chromosomes was higher, while in AML with monosomy 7 and deletion 5q the median expression of genes located in deleted regions was lower. The 50 most differentially expressed genes, as compared to all other subtypes, were equally distributed over the genome in AML subgroups with trisomies. In contrast, 30 and 86% of the most differentially expressed genes characteristic for AML with 5q deletion and monosomy 7 are located on chromosomes 5 or 7. In conclusion, gain of whole chromosomes leads to overexpression of genes located on the respective chromosomes. Losses of larger regions of the genome translate into lower expression of the majority of genes represented by only one allele. The reduced expression of these genes is the most characteristic difference in gene expression profiles between AML with monosomy 7 and AML with deletion 5q, respectively, and other AML subtypes. Therefore, these data provide evidence that gene dosage effects gene expression in AML with unbalanced karyotype abnormalities. Losses of specific regions of the genome determine the gene expression profile more strongly than the gain of whole chromosomes.Leukemia (2005) 19, 1224–1228. doi:10.1038/sj.leu.2403810 Published online 19 May 2005 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the study on the mutations of genes and cytogenetics in molecular writing of the patients with chronic myelomonocytic leukemia (CMML).

In acute myeloid leukemia (AML) with complex aberrant karyotype, a loss of one TP53 allele is frequently observed. We analyzed the incidence of TP53 mutations and deletions in 107 AML with complex aberrant karyotype. In 50 of 57 cases showing a loss of one TP53 allele, a TP53 mutation was detected in the remaining allele. In addition, in 33 of 50 cases with two TP53 copies, a TP53 mutation was found. Therefore, the frequency of TP53 mutations in AML with complex aberrant karyotype was 78%. In a second step, we analyzed TP53 mutations in a cohort of AML comprising different cytogenetic subgroups. TP53 mutations were detected in 33 of 235 cases (14%). Coincidences with other molecular mutations were rare. We confirmed a high incidence of TP53 mutations in AML with a complex aberrant karyotype (29/42, 69%) and demonstrated that TP53 mutations are very rare in AML without a complex aberrant karyotype (4/193, 2.1%). [ABSTRACT FROM AUTHOR]

The article presents a letter to the editor about a case of acute myeloid leukemia with a CHIC2-ETV6 fusiongen and multiple other molecular aberrations.

Presents a letter to the editor regarding acute myeloid leukemia.

Leukemia (2003) 17, 461–463. doi:10.1038/sj.leu.2402813 [ABSTRACT FROM AUTHOR]

During aging of human skin, a number of intrinsic and extrinsic factors cause the alteration of the skin's structure, function and cutaneous physiology. Many studies have investigated the influence of the skin microbiome on these alterations, but the molecular mechanisms that dictate the interplay between these factors and the skin microbiome are still not fully understood. To obtain more insight into the connection between the skin microbiome and the human physiological processes involved in skin aging, we performed a systematic study on interconnected pathways of human and bacterial metabolic processes that are known to play a role in skin aging. The bacterial genes in these pathways were subsequently used to create Hidden Markov Models (HMMs), which were applied to screen for presence of defined functionalities in both genomic and metagenomic datasets of skin-associated bacteria. These models were further applied on 16S rRNA gene sequencing data from skin microbiota samples derived from female volunteers of two different age groups (25-28 years ('young') and 59-68 years ('old')). The results show that the main bacterial pathways associated with aging skin are those involved in the production of pigmentation intermediates, fatty acids and ceramides. This study furthermore provides evidence for a relation between skin aging and bacterial enzymes involved in protein glycation. Taken together, the results and insights described in this paper provide new leads for intervening with bacterial processes that are associated with aging of human skin., Competing Interests: At the time of this study, KS and SS were employed by Estée Lauder Companies, a company that sells skin care products and hired NIZO (a contract research organization for (a.o.) microbiota studies) through authors WA, JB, RTE, SL, FdG and GAMK. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no further competing interests.

Background: Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. The primary objective of this phase I single center open label study was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the dual pan-class I PI3K and mTOR inhibitor BEZ235 in patients with advanced leukemia., Methods: Herein patients > 18 years of age who had relapsed or showed refractory leukemia were treated with BEZ235 (orally at 300-400 mg BID (cohort - 1/1)) to assess safety, tolerability, preliminary efficacy and pharmacokinetic (PK). Adverse events data and serious adverse events were analyzed and haematological and clinical biochemistry toxicities were assessed from laboratory test parameters. Response was assessed for the first time at the end of cycle 1 (day 29) and after every subsequent cycle. Pharmacokinetic and pharmacodynamic analyses of BEZ235 were also included (BEZ235 plasma levels, phosphorylation of AKT, S6 and 4EBP1). On statistics this trial is a multiple ascending dose study in which a following variant of the 3 + 3 rule ("Rolling Six"), a minimum of 6 and a maximum of 12 patients was recruited for the dose escalation and another 5 were planned for the expansion phase., Results: Twenty-four patients with ALL (n = 11) or AML (n = 12) or CML-BP (n = 1) were enrolled. All patients had failed one (n = 5) or more lines of therapy (n = 5) and 14 patients were in refractory / refractory relapse. No formal MTD was defined, stomatitis and gastrointestinal toxicity at 400 mg BID dose was considered incompatible with prolonged treatment. The RP2D of BEZ235 was defined as 300 mg BID. Four of 24 patients showed clinical benefit. Twenty-two of 24 patients discontinued because of progression, (median time to progression 27 days (4d-112d). There was no association between PK parameters and efficacy or tolerability., Conclusions: Combined inhibition of PI3K and mTOR inhibits a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML., Trial Registration: ClinicalTrials.gov , identifier NCT01756118. retrospectively registered 19th December 2012, https://clinicaltrials.gov/ct2/show/NCT01756118 .

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10 -3 and 36/67 (53%) and 53/67 (79%) at 10 -4 BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph + ALL.

Objectives: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high-dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99)., Patients and Results: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (P = .76), overall survival, event-free survival, leukemia-free survival, cumulative incidence of relapse at 6 years 75% vs 78% (P = .92); 75% vs 68% (P = .29); 86% vs 81% (P = .28); and 0% vs 12% (P = .04, no relapse vs four relapses), respectively. The median time to achieve molecular remission (RT-PCR negativity of PML-RARA) was 60 days in both arms (P = .12). The AMLCG regimen was associated with a longer duration of neutropenia (P = .02) and a higher rate of WHO grade ≥3 infections., Conclusions: The small number of patients limits the reliability of conclusions. With these restrictions, the outcomes of both approaches were similar and show the limitations of ATRA and chemotherapy. The HD ara-C-containing regimen was associated with a lower relapse rate in high-risk APL., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

BACKGROUND CML presenting with a variant Philadelphia translocation, atypical BCR-ABL transcript, additional chromosomal aberrations, and evolving MDS is uncommon and therapeutically challenging. The prognostic significance of these genetic findings is uncertain, even as singular aberrations, with nearly no data on management and outcome when they coexist. MDS evolving during the course of CML may be either treatment-associated or an independently coexisting disease, and is generally considered to have an inferior prognosis. Tyrosine kinase inhibitors (TKI) directed against BCR-ABL are the mainstay of treatment for CML, whereas treatment modalities that may be utilized for MDS and CML include allogeneic stem cell transplant and - at least conceptually - hypomethylating agents. CASE REPORT Here, we describe the clinical course of such a patient, demonstrating that long-term combined treatment with dasatinib and azacitidine for coexisting CML and MDS is feasible and well tolerated, and may be capable of slowing disease progression. This combination therapy had no deleterious effect on subsequent potentially curative haploidentical bone marrow transplantation. CONCLUSIONS The different prognostic implications of this unusual case and new therapeutic options in CML are discussed, together with a review of the current literature on CML presenting with different types of genomic aberrations and the coincident development of MDS. Additionally, this case gives an example of long-term combined treatment of tyrosine kinase inhibitors and hypomethylating agents, which could be pioneering in CML treatment.

Acute myeloid leukemia (AML) can be grouped into morphologically or genetically defined subtypes. Today, the AML phenotype-genotype associations, that is, FAB/WHO (French-American-British/World Health Organization) definitions and recurrent molecular mutations, are not fully understood. Therefore, we evaluated the impact of molecular mutations on the AML differentiation stage by molecular profiling of 4373 adult de novo AML patients in 7 cytomorphological subtypes. We investigated mutations in 20 genes, including myeloid transcription factors (CEBPA, RUNX1), tumor suppressors (TP53, WT1), DNA modifiers (DNMT3A, IDH1/2, TET2), chromatin modifiers (ASXL1, MLL), signal transduction genes (FLT3, KRAS, NRAS) and NPM1. The most frequently mutated genes per cytomorphological subtype were RUNX1 in M0 (43%), NPM1 in M1 (42%), DNMT3A in M2 (26%), NPM1 in M4 (57%), M5a (49%) and M5b (70%) and TP53 in M6 (36%). Although some gene mutations were frequent in several cytomorphological subtypes, a series of associations of co-occurring mutations with distinct phenotypes were identified for molecularly defined subcohorts. FLT3, NPM1 and WT1 mutations were associated with an immature phenotype in myeloblastic AML, whereas other combinations involving ASXL1, RUNX1, MLL-PTD, CEBPA or KRAS were more frequent in myeloblastic AML with maturation. Within the NPM1 mutated subcohort, ASXL1 mutations were significantly associated with a monoblastic differentiation and DNMT3A mutations with a monocytic phenotype.

High BAALC gene expression has been associated with poor prognosis in cytogenetically normal acute myeloid leukaemia (CN-AML) and has been suggested as a suitable marker for assessing minimal residual disease (MRD). The purpose of this study was to substantiate these findings by the analysis of a large data set of 632 diagnostic and follow-up samples in 142 intensively treated CN-AML patients. Paired diagnostic/relapse samples of 35 patients revealed stable high BAALC expression in 89%, irrespective of a high proportion of clonal evolution found in 49% of these cases. High BAALC expression, both directly after induction chemotherapy and within 3-6 months after induction chemotherapy, correlated significantly with shorter event-free survival and overall survival. Moreover, 8 of 10 patients displaying high BAALC expression levels after completion of induction therapy as well as 5 of 5 patients exhibiting high BAALC expression levels within 3-6 months after induction chemotherapy experienced relapse with a median of 197 and 101 days, respectively, from sampling to relapse. Thus, BAALC expression-based MRD detection during therapy may be considered a strategy to identify patients at high risk of relapse., (© 2016 John Wiley & Sons Ltd.)