多发性骨髓瘤治疗后继发骨髓增生异常综合征一例并文献复习

目的：探讨多发性骨髓瘤（MM）治疗后继发骨髓增生异常综合征（MDS）患者的临床特点,提高对这两种疾病的认识。方法分析1例 MM 继发 MDS 的患者,对 MM 诊断和治疗以及演变为 MDS后的临床特点进行总结,并复习相关文献。结果该例患者初诊为 MM 2年4个月后,经临床、骨髓形态学、流式细胞术及荧光原位杂交（FISH）检查,确诊为 MDS-难治性贫血伴原始细胞增多-Ⅱ（MDS-RAEB-Ⅱ）。结论 MM 继发 MDS 病例报道少见,转为 MDS 后可进一步转化为急性髓系白血病（AML）,较原发性AML 具有更强的耐药性,预后差。     

CAT方案治疗难治性急性髓系白血病的临床观察

目的：初步观察CAT(环磷酰胺、阿糖胞苷、拓扑替康)方案对难治性急性髓系白血病(AML)的近期临床疗效并评价此方案的不良副作用。方法：选择8例难治性AML(原发难治性AML3例，AML伴多系形态发育异常，此前有MDS病史患者3例，慢性粒细胞白血病AML变2例)．应用CAT方案治疗，其中4例治疗1疗程，其余4例治疗2疗程。结果：1例在骨髓抑制期死于感染性休克．可评价疗效7例，1例达完全缓解(CR)，3例达部分缓解(PR)，1例CML急变患者经2疗程后回到慢性期，总有效率71．4％(5/7例)，中位生存期为6．5(0．3—22^ )个月。主要不良副作用为骨髓抑制。结论：CAT方案为高危MDS、加速／急变期CML和继发于MDS的AML患者的一个有效且毒性可耐受的治疗新方案。     

AML/TMDS与MDS-AML的对比研究

目的 :分析三系病态造血的急性髓系白血病 (AML/TMDS)与骨髓增生异常综合征演变为急性髓系白血病 (MDS AML)的差异。方法 :采用常规形态学和细胞化学染色方法观察患者外周血和骨髓细胞。结果 :AML/TMDS患者血小板计数和外周原始细胞百分率高于MDS AML(P <0 0 5 ,P <0 0 1) ;小巨核细胞和Pseudo pelger异常明显低于MDS AML(P <0 0 5 ,P <0 0 1) ,2组病例MPO染色阳性率基本一致 ,但AML/TMDS患者MPO积分显著高于MDS AML(P <0 0 1)。AML/TMDS患者多核原始红细胞明显低于MDS AML(P <0 0 5 ) ;AML/TMDS与MDS AML患者巨大血小板分别为 2 3 1%和 86 7%。结论 :AML/TMDS与MDS AML白血病克隆不同 ,正确诊断对确定方案、判断疗效及预后有重要意义     

AML／TMDS与MDS—AML的对比研究

目的：分析三系病态造血的急性髓系白血病(AML／TMDS)与骨髓增生异常综合征演变为急性髓系白血病(MDS—AML)的差异。方法：采用常规形态学和细胞化学染色方法观察患者外周血和骨髓细胞。结果：AML/TMDS患者血小板计数和外周原始细胞百分率高于MDS—AML(P＜0．05，P＜0．01)；小巨核细胞和Pseudo-pelger异常明显低于MDS-AML(P＜0．05，P＜0．01)，2组病例MPO染色阳性率基本一致，但AML/TMDS患者MPO积分显著高于MDS—AML(P＜0．01)。AML/TMDS患者多核原始红细胞明显低于MDS—AML(P＜0．05)；AML／TMDS与MDS—AML患者巨大血小板分别为23．1％和86．7％。结论：AML/TMDS与MDS—AML白血病克隆不同，正确诊断对确定方案、判断疗效及预后有重要意义。     

由骨髓增生异常综合征转化的急性髓系白血病出现费城染色体一例并文献复习

目的 探讨由骨髓增生异常综合征(MDS)转化的急性髓系白血病(AML)出现费城染色体(Ph)的特点.方法 对1例血小板减少患者的骨髓形态学、组织学、免疫学、细胞遗传学、分子生物学等结果进行追踪观察,并复习相关文献.结果 该患者血小板单系减少,无肝脾大,骨髓巨核细胞成熟障碍,血小板相关抗体阴性,正常染色体核型,对糖皮质激素治疗无反应;7个月后出现骨髓巨核细胞病态造血以及+8染色体;21个月后进展为AML,出现包含t(9;22)(q34;q11.2)的复杂染色体以及bcr-abl融合基因,采用伊马替尼联合HA、CAG方案化疗无反应.结论 由MDS转化的AML出现Ph染色体非常罕见,与MDS疾病进展以及不良预后有关.     

骨髓中CDKN1C阳性表达在MDS和AML患者中检测的临床意义

目的 探讨骨髓中CDKN1C阳性表达在骨髓增生异常综合征(MDS)和继发性急性髓系白血病(AML)患者中检测的临床意义。方法 选取125例MDS/AML患者作为研究对象,同时选取20例健康人群作为健康对照组,分析MDS/AML患者骨髓CD34⁺细胞中CDKN1C的mRNA和蛋白表达水平,比较不同CDKN1C表达水平的MDS患者生存率,采用Cox回归分析MDS和AML患者生存率影响因素,并分析治疗方法对不同CDKN1C表达水平的MDS患者生存率的影响。结果 MDS/AML患者骨髓CD34⁺细胞中CDKN1C mRNA和蛋白表达水平显著高于健康对照组,且与BM(Bone marrow)比例呈正相关(r=0.423,P=0.012);CDKN1C高表达组患者的生存率显著低于CDKN1C低表达组和CDKN1C中表达组(P＜0.05);Cox回归分析结果显示高龄、高BM比例、细胞遗传学风险差以及CDKN1C阳性显著影响MDS/AML患者生存率(P＜0.05);MDS/AML化疗的CDKN1C阳性表达组患者生存率显著低于CDKN1C阴性组患者(P＜0.05),MDS/AML化疗后造血干细胞移植(AlloSCT)的CDKN1C阳性组患者生存率显著低于CDKN1C阴性组患者(P＜0.05)。结论 MDS/AML患者骨髓中CDKN1C的表达显著增高,CDKN1C阳性表达显著影响化疗MDS/AML患者的预后生存。     

伴rob(13;22)(q10;q10)的治疗相关急性髓系白血病1例并文献复习

目的提高对治疗相关急性髓系白血病(AML)的认识。方法回顾性分析烟台毓璜顶医院收治的1例横纹肌肉瘤治疗后继发AML伴染色体核型rob(13;22)(q10;q10)患儿的临床资料,并进行文献复习。结果该例女性患儿6岁5个月,在2018年1月诊断为横纹肌肉瘤,接受规范化疗30个月后确诊为治疗相关AML,染色体核型45,XX,t(11;19)(q23;q13),rob(13;22)(q10;q10),融合基因MLL⁃ELL阳性。接受DA(阿糖胞苷+柔红霉素)方案化疗后无明显改善,家属放弃治疗,患儿死亡。结论治疗相关AML多与应用鬼臼毒素类(依托泊苷等)药物化疗、联合放疗等因素有关。具有高危细胞遗传学因素的治疗相关AML预后差。     

再生障碍性贫血和克隆演变:种系和体细胞遗传学

对于骨髓衰竭(BMF)的患者,克隆演变为骨髓增生异常综合征(MDS)或急性髓系白血病(AML)仍然是一个严重的并发症.明确演变为MDS或者AML的危险因素可以为个体化治疗方案提供信息,并确定早期或前期进行造血干细胞移植可能受益的患者.目前,临床实验室可以进行二代DNA测序,研究集中在种系和体细胞突变对BMF患者诊断和监测的应用.大多数种系遗传性BMF疾病具有高倾向MDS或AML转化的特征.近来BMF的体细胞突变研究发现高频的克隆性造血干细胞具有获得性基因突变,这些基因与MDS或AML相关.文章就第58届美国血液学会(ASH)年会中对于BMF患者进展为克隆性疾病的种系和体细胞突变的评价以及临床基因检测的挑战进行介绍.     

地西他滨联合异基因造血干细胞微移植治疗骨髓增生异常综合征转急性髓系白血病一例

患者 男性,69岁.因发现贫血5年,加重1个月余就诊.患者于2008年体检时发现贫血,血红蛋白86 g/L,骨髓穿刺提示：红系病态造血,伴环状铁粒幼细胞超过0.15,诊断骨髓增生异常综合征（myelodysplasia syndrome,MDS）-难治性贫血伴环形铁幼细胞增多（refractory anemia with ring sideroblastsa,RARS）,当时未治疗,血红蛋白波动于80～90 g/L.2013年1月开始全血细胞减少,骨髓穿刺提示：粒系、红系病态造血,环形铁粒幼红细胞0.38,诊断MDS-难治性血细胞减少伴有多系发育异常（refractory cytopenia with mulfilineage dysplasia,RCMD）。     

骨髓涂片结合活组织检查切片诊断骨髓增生异常综合征6例

 【摘要】　目的　探讨骨髓涂片结合活组织检查切片对诊断骨髓增生异常综合征（MDS）的意义。 方法　回顾性分析6例MDS患者临床资料。以骨髓涂片结合活组织检查切片进行定期监测,以便进一步判断疾病的演变。 结果　6例患者从发病到确诊为2～17个月。按世界卫生组织（WHO）分类标准诊断,难治性血细胞减少伴多系发育异常（RCMD）2例,难治性贫血伴原始细胞增多（RAEB）I型1例,Ⅱ型3例。经历1~12个月转化为急性髓系白血病（AML）3例。按国际预后积分系统（IPSS）分为中危1组和2组共5例,高危组1例。死亡3例。 结论　MDS的发生是一个不断演进的过程,骨髓涂片结合活组织检查切片可观察骨髓细胞发育异常形态学表现、原始细胞比例和骨髓增生程度的变化,从而有助于MDS的诊断。     

Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia.

The role of internal tandem duplication of fms-like tyrosine kinase 3 (FLT3/ITD), mutations at tyrosine kinase domain (FLT3/TKD) and N-ras mutations in the transformation of myelodysplastic syndrome (MDS) to AML was investigated in 82 MDS patients who later progressed to AML; 70 of them had paired marrow samples at diagnosis of MDS and AML available for comparative analysis. Five of the 82 patients had FLT3/ITD at presentation. Of the 70 paired samples, seven patients acquired FLT3/ITD during AML evolution. The incidence of FLT3/ITD at diagnosis of MDS was significantly lower than that at AML transformation (3/70 vs 10/70, P<0.001). FLT3/ITD(+) patients progressed to AML more rapidly than FLT3/ITD(-) patients (2.5+/-0.5 vs 11.9+/-1.5 months, P=0.114). FLT3/ITD(+) patients had a significantly shorter survival than FLT3/ITD(-) patients (5.6+/-1.3 vs 18.0+/-1.7 months, P=0.0008). After AML transformation, FLT3/ITD was also associated with an adverse prognosis. One patient had FLT3/TKD mutation (D835Y) at both MDS and AML stages. Additional three acquired FLT3/TKD (one each with D835 H, D835F and I836S) at AML transformation. Five of the 70 matched samples had N-ras mutation at diagnosis of MDS compared to 15 at AML transformation (P<0.001), one lost and 11 gained N-ras mutations at AML progression. Coexistence of FLT3/TKD and N-ras mutations was found in two AML samples. N-ras mutations had no prognostic impact either at the MDS or AML stage. Our results show that one-third of MDS patients acquire activating mutations of FLT3 or N-ras gene during AML evolution and FLT3/ITD predicts a poor outcome in MDS.     

Therapy‐related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide,vincristine, doxorubicin,and dexamethasone regimens

BACKGROUND:

Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children.

METHODS:

A total of 641 patients with de novo ALL who were treated with the hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed.

RESULTS:

Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo‐diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper‐CVAD in 7 patients, hyper‐CVAD with rituximab in 8 patients, and hyper‐CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was ?5, ?7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline–based treatment was given to 12 patients with AML and high‐risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5–11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months).

CONCLUSIONS:

Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper‐CVAD regimens, and response to therapy is poor. Cancer 2009. © 2008 American Cancer Society.     

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome

BACKGROUND:

Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline‐based induction therapy.

METHODS:

This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS).

RESULTS:

The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%‐71%), and median OS was 6.5 (95% CI, 3.9‐8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04‐0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38‐13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01).

CONCLUSIONS:

Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy. Cancer 2011. © 2010 American Cancer Society.     

Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine

TP53 mutations are found in 5–10% of MDS and AML, where they are generally associated with complex karyotype and an overall poor prognosis. However, the impact of TP53 mutations in MDS treated with azacitidine (AZA) remains unclear. We analyzed TP53 mutations in 62 patients with high risk MDS or AML treated with AZA. A TP53 mutation was found in 23 patients (37.1%), associated with complex karyotype in 18 (78.3%) of them. TP53 mutations had no significant impact on response or complete response to AZA (p = 0.60 and p = 0.26, respectively). By univariate analysis, OS was negatively influenced by the presence of TP53 mutation (median OS 12.4 months versus 23.7 months, p < 10⁻⁴), abnormal cytogenetics (median OS 14.4 months vs 33 months, p = 0.02) complex cytogenetics (median OS 12.7 months versus 23.7 months, p = 0.0005), and a diagnosis of AML (median 14.5 months vs 21.2 months for MDS or CMML, p = 0.02). By multivariate analysis, only TP53 mutational status (HR 2.89 (95% confidence interval 1.38–6.04; p = 0.005) retained statistical significance for OS. Results were similar when the analysis was restricted to MDS and CMML patients, excluding AML (HR = 2.46 (95% confidence interval: 1.1–6.4); p = 0.04)).     

Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone-based therapy for breast carcinoma

Of 1774 patients with breast cancer given mitoxantrone (MTZ) with methotrexate (n = 492) or with methotrexate and mitomycin C (n = 1282), nine developed MDS/AML after a median of 2.5 years. Median duration of survival from diagnosis of MDS/AML was 10 months and six patients died. The crude incidence of developing MDS/AML after MMM or MM chemotherapy was 15 per 100,000 patient years follow-up, while the actuarial risk was 1.1% and 1.6% at 5 and 10 years respectively. MTZ-based regimens carry a 10 x higher risk of subsequent MDS/AML compared to that seen in the general population.     

儿童白血病患者Flt-3/ITD突变分析及其临床意义

背景与目的:Flt-3跨膜区内部串联重复(Flt-3 intemal tandem duplication,Flt-3/ITD)突变是近年来发现的Flt-3基因最常见的一种突变类型,是急性髓系白血病(acute myeloid leukaemia,AML)中发生率最高且与预后相关的突变.本研究旨在探讨Flt-3/ITD突变与儿童白血病发生的关系及其临床意义.方法:采用聚合酶链反应(polymerase chain reaction,PCR)联合序列测定,检测302例儿童白血病患者骨髓Flt-3/ITD突变情况,其中包括AML 122例、急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)124例、幼年型慢性粒细胞白血病(juvenile chronic myelogenous leukemia,JCML)17例和骨髓异常增生综合征(myelodysplastic syndromes,MDS)39例.结果:122例AML患者中98例(80.33%)Flt-3阳性;21例(17.21%)发生Flt-3/ITD突变,分别为M0 3例、M1 2例、M2 4例、M4 8例及M5 4例,突变率分别为42.86%(3/7)、22.22%(2/9)、12.90%(4/31)、44.44%(8/18)和15.38%(4/26).此外,124例ALL中72例Flt-3阳性,阳性率为58.06%,其中2例发现Flt-3/ITD突变,突变率1.61%.测序及Blast比对分析显示,外显子11区均有ITD,各例ITD的复制区域不同,长短不等(24～95 bp).39例MDS和17例JCML患者中均未检测到Flt-3/ITD突变.临床资料显示,21例Flt-3/ITD突变的AML患者中有19例在短期内死亡,这19例的中位生存时间为13.5个月(0～47个月),死亡率为90.48%,与无Flt-3/ITD突变患者相比有显著性差异(P＜0.05).Flt-3/ITD突变阳性患者外周血中性粒细胞平均比率与Flt-3/ITD突变阴性患者无显著性差异(P＞0.05).染色体核型分析显示,Flt-3/ITD的AML患者中3例存在有染色体异位,分别为t(11;12)(p15;q13)、t(6;9)(p23;q23)、inv16(q21;q23).结论:Flt-3/ITD突变多发现于AML,罕见于ALL,未见于MDS和JCML.该突变与儿童白血病特别是儿童AML的发生及进展有关.Flt-3/ITD可以作为判断AML预后的重要标志之一.     

Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: a report from the German Hodgkin's Lymphoma Study Group.

PURPOSE: To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin's disease (HD). PATIENTS AND METHODS: Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9). RESULTS: A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)-containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS. CONCLUSION: The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication.     

Better detection of FLT3 internal tandem duplication using peripheral blood plasma DNA.

Somatic mutation of the FLT3 gene as an internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence causes constitutive tyrosine phosphorylation and activation. Tumor-specific DNA has been documented in the sera of patients with solid tumors even when it is in an early stage. We compared the detection of FLT3 ITD in DNA extracted from cells of bone marrow (BM) aspirations with DNA extracted from peripheral blood (PB) plasma in patients newly diagnosed with acute myeloid leukemia (AML; 85 patients), myelodysplastic syndrome (MDS; 16 patients), and acute lymphocytic leukemia (ALL; 16 patients). FLT3 ITD was detected in 18 (21%) AML samples and in one (6%) MDS sample in both cellular and plasma DNA but in none of the ALL samples. Hemizygous/homozygous FLT3 ITD was detected in five (28%) of the FLT3 ITD-positive AML using plasma DNA, whereas only four of these cases showed hemizygous/homozygous FLT3 ITD using cellular DNA. The presence of FLT3 ITD was associated with significantly shorter survival (P = 0.02) when only patients younger than 50 years of age (48 AML+MDS patients) were considered. This finding was independent of cytogenetics in this age group. However, patients with the FLT3 ITD hemizygous/homozygous phenotype had even shorter survival (P = <0.001). As expected, the presence of FLT3 ITD correlated with higher white blood cell (WBC) counts. These data demonstrate that plasma DNA is a reliable alternative resource for detecting FLT3ITD, especially the hemizygous/homozygous genotype. Furthermore, the data derived from this study support the notion that the presence of FLT3 ITD in conjunction with the absence of the wild-type FLT3 allele predicts an especially poor prognosis for patients with AML.     

Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes

Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications.