Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Clinical Effects of Venetoclax in the Treatment of Acute Myeloid Leukemia in the Elderly

Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from January 2022 to January 2024 were selected, including 38 cases of patients whose primary treatment was not suitable for intensive chemotherapy and 12 cases of relapsed/refractory AML patients, to observe the therapeutic efficacy and safety of venetoclax. Results: Among the 38 patients whose primary treatment was not suitable for intensive chemotherapy, 5 cases were treated with venetoclax monotherapy, 33 cases were treated with venetoclax + azacitidine, and 25 patients (65.79%) achieved complete remission (CR) with incomplete hematologic recovery (CRi) after 28 days of treatment;10 patients with relapsed/refractory AML were treated with venetoclax + azacitidine, and 2 patients were treated with venetoclax + azacitidine + chemotherapy, and 2 patients achieved optimal therapeutic response after 28 days of treatment and CR/CRi was achieved in 7 patients (58.33%). There were 47 (94.0%) patients with grade 3 or higher granulocytopenia, 46 (92.0%) patients with hemoglobin reduction, and 43 (86.0%) patients with thrombocytopenia, developed after 28 days of treatment. 11 patients developed infections after treatment and there was one case of tumor lysis syndrome. Conclusion: The response rate of venetoclax monotherapy and combination in elderly AML induction therapy is high, and the overall tolerability of elderly patients is good, so it can be popularized and applied.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.Methods SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or cytarabine.Cell viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow cytometry.Western blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using siRNA.Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A knockdown.Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells.The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation.MT2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 cells.In addition,metformin inhibited cell growth and induced apoptosis in SKM-1 cells.Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine.Furthermore,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Adult rhabdomyosarcoma combined with acute myeloid leukemia: A case report

BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies.CASE SUMMARY We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia.Further disease progression was observed after multiline chemotherapy.Eventually,the patient suffered cerebral hemorrhage,which resulted in death.CONCLUSION The incidence of rhabdomyosarcoma in adults is extremely low,and secondary leukemia caused by rhabdomyosarcoma is even rarer.Secondary leukemia has a very poor prognosis and a low overall survival rate.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

Posaconazole-associated severe hyperbilirubinemia in acute myeloid leukemia following chemotherapy: A case report

BACKGROUND Posaconazole is a widely used azole antifungal agent, and posaconazole-associated severe hyperbilirubinemia is usually rare in clinical practice. We herein report a 58-year-old male with acute myeloid leukemia, who developed fungal infection following chemotherapy.CASE SUMMARY After administration of posaconazole oral suspension, the patient developed severe hyperbilirubinemia and jaundice(Common Terminology Criteria for Adverse Events, CTCAE-Grade 3) with a serum total bilirubin(T-BIL) peak level of 170 μmol/L, alkaline phosphatase level of 739 U/L, alanine aminotransferase level of 99 U/L, and gamma-glutamyl transpeptidase level of 638 U/L. After posaconazole withdrawal and symptomatic treatment with liver-protective agents, the level of T-BIL and other laboratory data decreased gradually, and related symptoms disappeared. After medication analysis and literature review, we consider that the patient had a cholestatic type of posaconazoleinduced liver injury, which was related to intracellular mitochondrial DNA damage. The case demonstrates that when patients with hematological malignancy develop severe infection following chemotherapy, combination of anti-infective drugs may contribute to ahigher risk of severe drug-induced liver injury. CONCLUSION This is the first thoroughly documented case report of posaconazole-associated severe hyperbilirubinemia. Therefore, in order to avoid severe adverse events, liver and renal function should be monitored closely before and during the administration of posaconazole.

Therapy-Related Acute Myeloid Leukemia in A Primary Pulmonary Leiomyosarcoma Patient with Skin Metastasis

Primary pulmonary leiomyosarcoma （LMS） is a very unusual tumor.Although LMS has well-known metastatic potential,cutaneous metastasis is a remarkably uncommon.Exposure to cytotoxic agents could lead to ＂therapy-related myeloid neoplasm＂ （t-MN）.Starting from 2008,the World Health Organization （WHO） has adopted the term to cover the spectrum of malignant diseases previously known as therapy-related acute myeloid leukemia （t-AML）,therapy-related myelodysplastic syndrome （t-MDS） and therapy-related myelodysplastic/myelo-proliferative neoplasm （t-MDS/MPN）.We described the onset of t-MDS and progression to t-AML in one case diagnosed as primary pulmonary LMS with cutaneous metastasis.This patient achieved complete remission （CR） after three courses of IA regimen chemotherapy （idarubicin 5 mg/d,d 1-3;cytarabine 100 mg/d,d 1-5） and 1 course of HA chemotherapy regimen （homoharringtonine 3 mg/d,d 1-3;cytarabine 100 mg/d,d 1-7）.This case presents the natural course of therapy-related neoplasm and provides therapeutic experience for t-AML.

Role of autophagy in acute myeloid leukemia therapy

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Comparison of Mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL Acute Myeloid Leukemia Patients with Favorable and Intermediate Cytogenetics

In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine（HAM） with that of high-dose cytarabine alone（Hi DAC） as consolidation regimens in non-acute promyelocytic leukemia（APL） acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People＇s Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission（CR1）.In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival（RFS） and overall survival（OS） were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.

The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells

Background:Current chemotherapy for acute myeloid leukemia(AML)mainly involves cytotoxic agents such as doxorubicin(DNR),mitoxantrone(Mito)or 2‐aminopurine‐6‐thiol(6‐TG).However,because these agents are relatively ineffective,discovering other more effective drugs for AML treatment would be valuable.Methods:The in vitro antitumor effect of lenvatinib on AML cells was examined using the colorimetric MTT assay for assessing cell metabolic activity.AML cells mixed with Poloxamer 407 were injected into nude mice to form subcutaneous tumors.Tumorbearing mice received lenvatinib by oral administration.The antitumor effect of lenvatinib was established by measuring tumor volumes and weights.Results:Lenvatinib inhibited the growth of AML cells in a dose‐dependent manner.We used AML cells to establish subcutaneous tumor tissues by mixing the cell suspension with Poloxamer 407.Poloxamer 407 alone did not influence the subcutaneous growth of AML cells.Treatment of lenvatinib inhibited in vivo tumor growth of AML cells.Conclusion:The multiple‐kinase inhibitor lenvatinib inhibits the in vitro proliferation of AML cells,and restricts the in vivo growth of AML tumors.

Blood typing and transfusion therapy in a patient with A2 subtype acute myeloid leukemia M2:A case report

BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML can be very effective for some patients,yet it leaves others with serious and even life-threatening side effects.Chemotherapy is still the primary treatment for most AML,but over time,leukemia cells become resistant to chemotherapy drugs.In addition,stem cell transplantation,targeted therapy,and immunotherapy are currently available.At the same time,with the progression of the disease,the patient may have corresponding complications,such as coagulation dysfunction,anemia,granulocytopenia,and repeated infection,so transfusion supportive therapy will be involved in the overall treatment regime.To date,few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2.Blood transfusion therapy is an important supportive treatment for AML-M2,and accurate determination of patients'blood type is one of the most important steps in the treatment process.In this study,we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients.CASE SUMMARY In order to determine the blood type of the patient,serological and molecular biological methods were used for reference tests,and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment.According to the results obtained by serological and molecular biological methods,the blood type of the patient was A2 subtype;the genotype was A02/001;the irregular antibody screening was negative,and anti-A1 was found in the plasma.According to the overall treatment plan,active anti-infection,elevated cells,component blood transfusion support,and other rescue and supportive treatments were given,and the patient successfully passed the stage of myelosuppression after chemotherapy.Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs,and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype(residual leukemia cells<10-4).CONCLUSION The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.

Gemtuzumab ozogamicin in the treatment of adult acute myeloid leukemia

Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to a derivative of an antitumor antibiotic, calicheamicin. GO was approved for the treatment of relapsed acute myeloid leukemia (AML) in the United States (US) in 2000. However, GO was withdrawn from the US market in June 2010, because a large-scale clinical trial failed to show additive or synergistic effects with conventional chemotherapy for newly diagnosed AML. GO is currently available only in Japan. However, several large clinical studies have demonstrated beneficial effects of GO when added to chemotherapy for AML in recent years;therefore, reconsideration of GO availability is gaining attention. Therefore, the role and efficacy of GO as monotherapy or in combination therapy for de novo or relapsed AML should be positively investigated.

Acute myeloid leukemia in the era of precision medicine:recent advances in diagnostic classification and risk stratification

Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

A phase Ⅳ study of homoharringtonine, cytarabine, aclacinomycin and G-CSF(HCAG) regimen compared with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia patients

Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia(AML) patients. Methods · Forty-one patients with AML(aged 55-71 years) were randomly divided into two groups(Group HCAG and Group IA) between 2014 and 2016 for induction and consolidation therapy. Multivariate analysis was applied to identify prognostic factors for relapse-free survival(RFS). Results · A total of 29 patients(70.7%) achieved complete remission(CR). The estimated 2-year overall survival(OS) was 66.8% in Group HCAG and 75.4% in Group IA(P=0.913). The estimated 2-year RFS was 61.8% in Group HCAG and 49.1% in Group IA(P=0.411). Age remained as the unfavorable prognostic factor, leading to significant differences in OS and RFS. In addition, RFS was influenced by cytogenetic/molecular risk stratification. Conclusion · Although HCAG seemed not to particularly benefit the group, the dose reduction of anthracyclines may be applied in elderly patients with comparable short-time outcome. Furthermore, the introduction of homoharringtonine resulted in an improvement of treatment response for more than 20% compared with CAG regimen.

Myeloid sarcoma of the colon as initial presentation in acute promyelocytic leukemia:A case report and review of the literature

BACKGROUND Myeloid sarcoma(MS)rarely occurs in acute promyelocytic leukemia(APL)at onset,but it can develop in relapse cases,especially after APL treated with alltrans retinoic acid(ATRA).Therefore little is known about the clinical features and suitable treatment for APL related MS due to the rarity of the disease,although this may be different from the treatment and prognosis of MS in the relapse stage.To our best knowledge,this is the second case report of APL initial presentation as colon MS.CASE SUMMARY A 77-year-old woman complained of intermittent right lower abdominal pain,black stool,and difficult defecation for 2 mo.Physical examination showed diffuse tenderness during deep palpation and an anemic appearance.Laboratory findings showed positivity for fecal occult blood testing;white blood cell count:3.84×109/L;hemoglobin:105 g/L;platelet count:174×109/L;and negativity for tumor markers.Abdominal enhanced computed tomography showed a space occupying lesion in the colon(1.9 cm).Fibrocolonoscopy revealed a polypoid and ulcerated mass measuring 2.5 cm.The tumor was removed.To our surprise,MS was confirmed by immunohistochemistry.PML/RARαfusion gene was detected in colon specimens by fluorescent in situ hybridization and real-time reverse transcription polymerase chain reaction,which was consistent with the bone marrow.She was diagnosed as having APL related MS.A smooth and unobstructed intestinal wall was found by fibrocolonoscopy,and continuous molecular remission was confirmed in both the bone marrow and colon after four courses of ATRA+arsenic trioxide(ATO).ATRA+ATO showed a favorable therapeutic response for both APL and MS.CONCLUSION Early use of ATRA can benefit APL patients,regardless of whether MS is the first or recurrent manifestation.

Targeting leukemia stem cells:The new goal of therapy in adult acute myeloid leukemia

The most popular view of hematopoietic cell lineage organization is that of complex reactive or adaptative systems.Leukemia contains a subpopulation of cells that display characteristics of stem cells.These cells maintain tumor growth.The properties of leukemia stem cells indicate that current conventional chemotherapy, directed against the bulk of the tumor,will not be effective.Leukemia stem cells are quiescent and do not respond to cell cycle-specific cytotoxic agents used to treat leukemia and thus contribute to treatment failure. New strategies are required that specifically target this malignant stem cell population.