AbstractAcute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors accompanied by a differentiation arrest. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its isolated loss increases mouse HSC self-renewal without malignant transformation.

摘要急性髓系白血病的特征是自我更新的髓系祖细胞不受控制的增殖，并伴有分化停滞。PHF6是在髓样白血病中突变的染色质结合蛋白，其分离的损失增加了小鼠HSC的自我更新而没有恶性转化。

We report here that Phf6 knockout increases the aggressiveness of Hoxa9-driven AML over serial transplantation, and increases the frequency of leukemia initiating cells. We define the in vivo hierarchy of Hoxa9-driven AML and identify a population that we term the “LIC-e” (leukemia initiating cells enriched) population.

我们在这里报道，Phf6敲除增加了Hoxa9驱动的AML相对于连续移植的侵袭性，并增加了白血病起始细胞的频率。我们定义了Hoxa9驱动的AML的体内层次结构，并确定了我们称之为“LIC-e”（白血病起始细胞富集）群体的群体。

We find that Phf6 loss expands the LIC-e population and skews its transcriptome to a more stem-like state; concordant transcriptome shifts are also observed on PHF6 knockout in a human AML cell line and in PHF6 mutant patient samples from the BEAT AML dataset. We demonstrate that LIC-e accumulation in Phf6 knockout AML occurs not due to effects on cell cycle or apoptosis, but due to an increase in the fraction of its progeny that retain LIC-e identity.

我们发现Phf6的丢失扩大了LIC-e种群，并使其转录组偏向于更像茎的状态；在人类AML细胞系和来自BEAT AML数据集的PHF6突变患者样品中，PHF6基因敲除也观察到一致的转录组变化。我们证明Phf6敲除AML中的LIC-e积累不是由于对细胞周期或细胞凋亡的影响，而是由于其保留LIC-e身份的后代比例的增加。

Our work indicates that Phf6 loss increases AML self-renewal through context-specific effects on leukemia stem cells..

我们的工作表明，Phf6的丢失通过对白血病干细胞的背景特异性作用增加了AML的自我更新。。

IntroductionPHF6 (Plant homeodomain-like finger protein 6) is an X-chromosome gene mutated in a variety of myeloid and lymphoid leukemias. PHF6 localizes to the nucleus and is known to interact with chromatin, but its precise molecular function is poorly understood, with reported roles ranging from cell cycle control [1,2,3], DNA repair [3, 4], to transcriptional regulation [5,6,7,8].

简介PHF6（植物同源结构域样手指蛋白6）是一种X染色体基因，在多种髓系和淋巴样白血病中发生突变。PHF6定位于细胞核，已知与染色质相互作用，但其确切的分子功能知之甚少，报道的作用范围从细胞周期控制[1,2,3]，DNA修复[3,4]到转录调控[5,6,7,8]。

Somatic PHF6 mutations are seen in 38% of T-cell acute lymphocytic leukemia (T-ALL) [9], in 3–6% of AML, myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML), and in 23% of mixed-phenotype acute leukemia (MPAL) and undifferentiated leukemia [10,11,12,13,14,15,16]. PHF6 mutations co-occur in MDS/AML with mutations in RUNX1, ASXL1, and U2AF1 [11, 13, 16], with the majority of PHF6 mutations being frameshift and nonsense mutations distributed throughout the gene body [16], predicted to produce null alleles and indicating that PHF6 acts as a leukemia suppressor.Germline Phf6 deletion in mice leads to perinatal lethality, while mice with hematopoietic Phf6 deletion are viable and fertile [17, 18].

体细胞PHF6突变见于38%的T细胞急性淋巴细胞白血病（T-ALL），3-6%的AML，骨髓增生异常综合征（MDS）和慢性粒单核细胞白血病（CMML），以及23%的混合表型急性白血病（MPAL）和未分化白血病[10,11,12,13,14,15,16]。PHF6突变与RUNX1，ASXL1和U2AF1突变共同发生在MDS/AML中[11，13，16]，大多数PHF6突变是移码突变和无义突变，分布在整个基因体中[16]，预计会产生无效等位基因，表明PHF6可作为白血病抑制因子。小鼠生殖系Phf6缺失导致围产期致死率，而造血Phf6缺失的小鼠是可行和可育的[17，18]。

Conditional hematopoietic knockouts using multiple Cre systems have consistently shown minimal alterations to homeostatic hematopoiesis, but striking increases in HSC self-renewal on transplantation, with the ability to engraft beyond five serial transplants without exhaustion, malignant transformation, or lineage skewing [17,18,19].

使用多个Cre系统的条件性造血敲除一直显示出对稳态造血的最小改变，但移植时HSC自我更新显着增加，能够移植超过五次连续移植而无衰竭，恶性转化或谱系偏斜[17，18，19]。

Phf6 knockout HSCs from aged mice show transcriptional profiles similar to young HSCs, and deletion of Phf6 from older mice shows a shift towards a younger HSC transcriptome [4]. Combination of Phf6 loss with overexpression of activating mutants of Notch1 [18] or Jak3 [20], or overexpression of wildtype Tlx3 [17] has been shown to cause T-ALL acceler.

来自老年小鼠的Phf6敲除HSC显示出与年轻HSC相似的转录谱，并且从老年小鼠中删除Phf6显示出向年轻HSC转录组的转变。Phf6缺失与Notch1（18）或Jak3（20）激活突变体的过表达或野生型Tlx3（17）的过表达相结合已被证明会引起T-ALL加速因子。

Phf6 loss increases leukemic disease burdenTo characterize the effect of Phf6 loss further, we analyzed peripheral blood, splenic architecture, and bone marrow leukemic cell burden of primary recipients at 8 weeks after transplantation. Mice transplanted with cKO+Hoxa9 cells showed a higher frequency of GFP+ cells in peripheral blood at 8 weeks than mice receiving Ctrl+Hoxa9 cells (Fig. 2A).

Phf6丢失会增加白血病疾病负担为了进一步表征Phf6丢失的影响，我们分析了移植后8周主要受者的外周血，脾脏结构和骨髓白血病细胞负担。移植cKO+Hoxa9细胞的小鼠在8周时外周血中GFP+细胞的频率高于接受Ctrl+Hoxa9细胞的小鼠（图2A）。

The cKO+Hoxa9 group also had greater leukocytosis (Fig. 2B) and more severe thrombocytopenia (Fig. 2C). Mice in both groups displayed comparable levels of anemia (Fig. S4A, B). The cKO+Hoxa9 group had increased spleen size and weight compared to the Ctrl+Hoxa9 group (Fig. 2D, E), and histopathological analysis showed greater effacement of splenic architecture (Fig. 2F).

cKO+Hoxa9组也有更大的白细胞增多（图2B）和更严重的血小板减少症（图2C）。两组小鼠的贫血水平相当（图S4A，B）。与Ctrl+Hoxa9组相比，cKO+Hoxa9组的脾脏大小和重量增加（图2D，E），组织病理学分析显示脾脏结构的消失更大（图2F）。

Splenic infiltration was quantified using a previously described leukemia infiltration score [28], and was found to be greater in cKO+Hoxa9 mice compared to Ctrl+Hoxa9 (Fig. 2G). Giemsa-stained cytospin preparations showed higher blast percentages in cKO+Hoxa9 at the 8-week timepoint (Fig. 2H, I), and flow cytometry showed higher absolute and percent GFP+ cells (Fig. 2J, S4C).

使用先前描述的白血病浸润评分（28）对脾脏浸润进行定量，发现与Ctrl+Hoxa9相比，cKO+Hoxa9小鼠的脾脏浸润更大（图2G）。吉姆萨染色的细胞离心涂片制剂在8周时间点显示cKO+Hoxa9中的爆炸百分比较高（图2H，I），流式细胞术显示GFP+细胞的绝对百分比和百分比较高（图2J，S4C）。

All GFP+ cells were myeloid for both groups (Fig. 2K, S4D). Thus, while mice from both groups succumbed at similar times after primary transplant (Fig. 1F), analyses at matched time points before the onset of mortality revealed greater disease burden in cKO+Hoxa9 mice compared to Ctrl+Hoxa9.Fig. 2: Phf6 loss increases leukemic disease burden.A–C Bar graphs showing peripheral blood analysis at 8 weeks after transplantation of Ctrl+Hoxa9 and cKO+Hoxa9 cells.

两组的所有GFP+细胞均为髓样（图2K，S4D）。因此，虽然两组小鼠在初次移植后的相似时间死亡（图1F），但在死亡发生前的匹配时间点进行的分析显示，与Ctrl+Hoxa9相比，cKO+Hoxa9小鼠的疾病负担更大。图2:Phf6损失增加白血病疾病负担。A–C条形图显示移植Ctrl+Hoxa9和cKO+Hoxa9细胞后8周的外周血分析。

A Percentage of GFP+ cells in peripheral blood. B, C Counts of (B) WBCs and (C) platelets in peripheral blood. Normal range for WBCs: 2000–10,000/µl. Normal range for platelets: 900–1600 × 10.

外周血中GFP+细胞的百分比。B、 C外周血中（B）WBC和（C）血小板的计数。白细胞的正常范围：2000–10000/µl。血小板的正常范围：900-1600×10。

Phf6 loss increases the frequency of self-renewing, transplantable LICsTo characterize the immunophenotype of AML subpopulations (including LICs), we further analyzed the marrow of Ctrl+Hoxa9 recipients at 8 weeks after transplantation. The GFP+ cells did not express B or T cell markers (Fig. S5A). Immature AML cells are known to have high c-Kit expression [29], and leukemic stem cells (LSCs) in the MLL-AF9 retroviral mouse model aberrantly express mature myeloid lineage antigens such as Ly6C and CD11b [30].

Phf6丢失增加了自我更新，可移植LIC的频率为了表征AML亚群（包括LIC）的免疫表型，我们在移植后8周进一步分析了Ctrl+Hoxa9受体的骨髓。GFP+细胞不表达B或T细胞标记（图S5A）。已知未成熟的AML细胞具有高c-Kit表达（29），MLL-AF9逆转录病毒小鼠模型中的白血病干细胞（LSCs）异常表达成熟的髓系抗原，如Ly6C和CD11b（30）。

To identify the corresponding subpopulation containing LICs in Hoxa9-only-driven AML, and to characterize the differentiation hierarchy of this model, we settled on a strategy using c-Kit and Ly6C expression to divide GFP+ marrow cells into three populations: (i) cKit+ Ly6C-, (ii) c-Kit+ Ly6C+, and (iii) c-Kit- Ly6C+ (Fig. 3A, S5B).

为了鉴定仅Hoxa9驱动的AML中含有LIC的相应亚群，并表征该模型的分化层次，我们确定了使用c-Kit和Ly6C表达将GFP+骨髓细胞分成三个群体的策略：（i）cKit+Ly6C-，（ii）c-Kit+Ly6C+，和（iii）c-Kit-Ly6C+（图3A，S5B）。

The population at the top of the hierarchy was the cKit+ Ly6C- population, an immature population with expression of cKit, CD34, and dim CD11b, with no expression of Ly6C, Ly6G, or Sca-1, and mixed expression of CD16/32 (Fig. S5C). This population was capable of giving rise to more differentiated Ly6C+ cells within 2 days of culture (Fig. S5D), could produce colonies on methylcellulose plating (Fig. 3B), and could engraft into recipient mice (Fig. 3C).

层次结构顶部的群体是cKit+Ly6C群体，这是一个不成熟的群体，表达cKit，CD34和dim CD11b，不表达Ly6C，Ly6G或Sca-1，并且混合表达CD16/32（图S5C）。该群体能够在培养2天内产生更多分化的Ly6C+细胞（图S5D），可以在甲基纤维素平板上产生菌落（图3B），并且可以植入受体小鼠（图3C）。

Based on this subpopulation’s ability to engraft, but cognizant that not all cells within it are LICs, we termed it the ‘LIC enriched’ (LIC-e) population (Fig. 3D). The second population was the c-Kit+ Ly6C+ population, also expressing CD11b, CD34, and CD16/32, but not Sca-1 (Fig. S5C). On culture, this population could only give rise to Ly6C+ cells, but not to any Ly6C- cells (Fig. S5D), indicating that it is irreversibly committed to differentiation.

基于该亚群的移植能力，但认识到其中并非所有细胞都是LIC，我们将其称为“富含LIC的”（LIC-e）群体（图3D）。第二个群体是c-Kit+Ly6C+群体，也表达CD11b，CD34和CD16/32，但不表达Sca-1（图S5C）。在培养中，该群体只能产生Ly6C+细胞，而不能产生任何Ly6C细胞（图S5D），表明它不可逆地致力于分化。

This population could produce a small.

这个人口可以产生一小部分。

Phf6 loss promotes a stemness gene networkWe determined the transcriptional consequences of Phf6 loss on Hoxa9-transformed marrow by performing RNA-Seq on LIC-e and committed leukemic cells from marrow of transplanted recipients at 8 weeks. Committed leukemic cells showed no change in gene expression with Phf6 loss (Fig. S6A, B, Table S2), while the LIC-e population showed 91 downregulated and 65 upregulated genes in cKO+Hoxa9 compared to Ctrl+Hoxa9 (Fig. 4A, B, Table S2).

Phf6丢失促进干性基因网络我们通过在8周时对LIC-e和来自移植受者骨髓的定型白血病细胞进行RNA-Seq来确定Phf6丢失对Hoxa9转化的骨髓的转录后果。定型白血病细胞显示Phf6缺失的基因表达没有变化（图S6A，B，表S2），而与Ctrl+Hoxa9相比，LIC-e群体在cKO+Hoxa9中显示91个下调和65个上调的基因（图4A，B，表S2）。

Genes downregulated in cKO+Hoxa9 LIC-e cells showed Gene Ontology (GO) enrichment for myeloid differentiation terms (Fig. 4C). Gene set enrichment analysis (GSEA) [31] showed that the cKO+Hoxa9 LIC-e transcriptome showed positive enrichment for genesets related to high LSC potential [32] and leukemic GMPs (L-GMPs) [33] and negative enrichment for genesets related to myeloid differentiation [34], and mature neutrophils and monocytes [35] (Fig. 4D, S6C).Fig.

在cKO+Hoxa9 LIC-e细胞中下调的基因显示出骨髓分化术语的基因本体论（GO）富集（图4C）。基因集富集分析（GSEA）显示，cKO+Hoxa9 LIC-e转录组对与高LSC电位（32）和白血病GMP（L-GMP）相关的基因组显示阳性富集，对与髓样分化（34）和成熟中性粒细胞和单核细胞（35）相关的基因组显示阴性富集（图4D，S6C）。图。

4: Phf6 loss promotes a stemness gene network.A Volcano plot showing differentially expressed genes in LIC-e cells from cKO+Hoxa9 compared to Ctrl+Hoxa9 bone marrow at 8 weeks after transplantation. (n = 3–4 biological replicates). B Heatmap of differential expression between Ctrl+Hoxa9 and cKO+Hoxa9 LIC-e cells.

4： Phf6丢失促进了干性基因网络。火山图显示移植后8周，与Ctrl+Hoxa9骨髓相比，来自cKO+Hoxa9的LIC-e细胞中差异表达的基因。（n=3-4个生物学重复）。B Ctrl+Hoxa9和cKO+Hoxa9 LIC-e细胞之间差异表达的热图。

Insets show selected downregulated (left) and upregulated (right) genes in cKO+Hoxa9 LIC-e compared with Ctrl+Hoxa9 LIC-e. C Top Gene Ontology terms enriched in genes downregulated in cKO+Hoxa9 LIC-e compared with Ctrl+Hoxa9 LIC-e. D Gene set enrichment analysis (GSEA) plots of the cKO+Hoxa9 LIC-e transcriptome compared to Ctrl+Hoxa9.

插图显示，与Ctrl+Hoxa9-LIC-e相比，cKO+Hoxa9-LIC-e中选择的下调（左）和上调（右）基因。与Ctrl+Hoxa9-LIC-e相比，cKO+Hoxa9-LIC-e中下调的基因富集的顶部基因本体术语。与Ctrl+Hoxa9相比，cKO+Hoxa9-LIC-e转录组的基因集富集分析（GSEA）图。

Plots show positive enrichment of gene sets related to high LSC frequency (left) and leukemic GMPs (middle), and negative enrichment of a gene set related to myeloid development (right). Normalized Enrichment .

图显示与高LSC频率（左）和白血病GMP（中）相关的基因组正富集，与骨髓发育相关的基因组负富集（右）。标准化富集。

Phf6 loss prevents exhaustion of LIC-e cells by maintaining their self-renewal potentialTo determine the kinetics of the effects of Phf6 loss on the behavior of LIC-e cells, we cultured Hoxa9-transduced mouse bone marrow in cytokine-supplemented media. The growth rate of bulk culture was similar for Ctrl+Hoxa9 and cKO+Hoxa9 marrow (Fig. S7A).

Phf6丢失通过维持其自我更新潜力来防止LIC-e细胞耗尽为了确定Phf6丢失对LIC-e细胞行为影响的动力学，我们在补充细胞因子的培养基中培养了Hoxa9转导的小鼠骨髓。Ctrl+Hoxa9和cKO+Hoxa9骨髓的批量培养生长速率相似（图S7A）。

When sorted LIC-e cells were cultured, most cells lost LIC-e identity within days (Fig. 5A). However, though both groups produced similar fractions of committed (c-Kit+ Ly6C+) and differentiated cells (c-Kit- Ly6C+), the Ctrl+Hoxa9 culture almost completely depleted its LIC-e population (<1%), while the cKO+Hoxa9 culture maintained this population, plateauing at 5–6% of the total culture after 5 days (Fig. 5A).

当培养分选的LIC-e细胞时，大多数细胞在几天内失去LIC-e身份（图5A）。然而，尽管两组产生的定型细胞（c-Kit+Ly6C+）和分化细胞（c-Kit-Ly6C+）的比例相似，但Ctrl+Hoxa9培养物几乎完全耗尽了其LIC-e群体（<1%），而cKO+Hoxa9培养物维持了这一群体，5天后稳定在总培养物的5-6%（图5A）。

Thus, Phf6 loss prevents exhaustion of the LIC-e population without impairing the rate of proliferation or differentiation of the bulk culture, recapitulating the in vivo LIC-e accumulation phenotype shown earlier (Fig. 3E–G).Fig. 5: Phf6 loss prevents exhaustion of LIC-e cells by maintaining their self-renewal potential.A Bar graph showing frequencies of subpopulations resulting from in vitro culture of LIC-e cells sorted 4 days after Hoxa9 transduction of Ctrl and cKO bone marrow.

因此，Phf6的丢失可以防止LIC-e种群的耗尽，而不会损害大量培养物的增殖或分化速率，从而重现了先前显示的体内LIC-e积累表型（图3E–G）。图5:Phf6损失通过维持其自我更新潜力来防止LIC-e细胞耗尽。条形图显示了在Hoxa9转导Ctrl和cKO骨髓后4天分选的LIC-e细胞的体外培养产生的亚群频率。

Inset bar graph depicts only LIC-e frequencies in the same culture. (n = 13 biological replicates). B Experimental design for study of in vitro cell cycle analysis (top) and self-renewal (bottom) of LIC-e cells using EdU chase and pulse-chase assay respectively. C Left, Bar graph showing frequencies of G0/G1, S, and G2/M phases in Ctrl+Hoxa9 and cKO+Hoxa9 LIC-e cells in culture 2 h after addition of EdU.

插图条形图仅描绘了同一文化中的LIC-e频率。（n=13个生物学重复）。B分别使用EdU追踪和脉冲追踪测定研究LIC-e细胞的体外细胞周期分析（顶部）和自我更新（底部）的实验设计。C左，条形图显示添加EdU后2小时培养物中Ctrl+Hoxa9和cKO+Hoxa9 LIC-e细胞中G0/G1，S和G2/M期的频率。

(n = 4–5 biological replicates) Right, Representative flow cytometry plots of same, with EdU marking cells in S phase and 7-AAD staining DNA. D .

（n=4-5个生物学重复）正确的，具有代表性的流式细胞术图，其中EdU标记细胞处于S期，7-AAD染色DNA。D。

Data availability

数据可用性

All generated datasets have been deposited to GEO: GSE270756.

所有生成的数据集都已保存到GEO:GSE270756。

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Download referencesAcknowledgementsWe thank Nancy Speck, Ivan Maillard, Wei Tong, and Kathrin Bernt for helpful discussions. VRP is supported by National Institute of Health (NIH) grant R01-HL155144 (NHLBI), American Cancer Society (ACS) grant 129784-IRG-16-188-38-IRG, an American Society of Hematology (ASH) Faculty Scholar Award, and a University of Pennsylvania Covid-19 Research Disruption Mitigation Fund.

下载参考文献致谢我们感谢Nancy Speck，Ivan Maillard，Wei Tong和Kathrin Bernt的有益讨论。VRP得到了美国国立卫生研究院（NIH）拨款R01-HL155144（NHLBI），美国癌症学会（ACS）拨款129784-IRG-16-188-38-IRG，美国血液学会（ASH）院士奖和宾夕法尼亚大学新型冠状病毒肺炎研究中断缓解基金的支持。

SSJ is supported by an ASH Restart Award. CA is supported by a Scholar Award from the American Society of Hematology (ASH) and Co-Operative Center for Excellence in Hematology (CCEH) grant by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Data for this manuscript were generated in the Penn Cytomics and Cell Sorting Shared Resource Laboratory at the University of Pennsylvania and is partially supported by the Abramson Cancer Center NCI Grant (P30 016520).

SSJ得到了ASH重启奖的支持。CA得到了美国血液学会（ASH）的学者奖和美国国家糖尿病、消化和肾脏疾病研究所（NIDDK）的血液学卓越合作中心（CCEH）的资助。这份手稿的数据是在宾夕法尼亚大学的宾夕法尼亚细胞组学和细胞分选共享资源实验室生成的，并得到了艾布拉姆森癌症中心NCI拨款（P30 016520）的部分支持。

The research identifier number is RRid: SCR_022376.Author informationAuthor notesThese authors contributed equally: Sapana S. Jalnapurkar, Aishwarya S. Pawar.Authors and AffiliationsDivision of Hematology and Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USASapana S.

研究标识符编号为RRid:SCR\U 022376。作者信息作者注意到这些作者做出了同样的贡献：Sapana S.Jalnapurkar，Aishwarya S.Pawar。作者和附属机构宾夕法尼亚大学佩雷尔曼医学院医学系血液学和肿瘤学系，宾夕法尼亚州费城，USASapana S。

Jalnapurkar, Aishwarya S. Pawar, Charles Antony, Patrick Somers, Jason Grana, Victoria K. Feist & Vikram R. ParalkarBiomedical Graduate Studies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USAAishwarya S. PawarInstitute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USASubin S.

Jalnapurkar，Aishwarya S.Pawar，Charles Antony，Patrick Somers，Jason Grana，Victoria K.Feist＆Vikram R.ParalkarBiomedical研究生，宾夕法尼亚大学佩雷尔曼医学院，宾夕法尼亚州费城，USAishwarya S.PawarInstitute for Biomedical Informatics，宾夕法尼亚大学佩雷尔曼医学院，宾夕法尼亚州费城，USASubin S。

GeorgeDepartment of Pathology, University of Chicago, Chicago, IL, USASandeep GurbuxaniDepartment of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine,.

美国伊利诺伊州芝加哥市芝加哥大学乔治病理学系宾夕法尼亚大学佩雷尔曼医学院细胞与发育生物学系，。

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PubMed Google ScholarContributionsVRP conceived the project and supervised the study. SSJ designed and performed a majority of experiments, with additional studies by AP and PS. SSJ, AP, and VRP wrote the manuscript with input from all authors. SSG, SSJ, and AP performed bioinformatic analyses, including scripting for downstream analysis and graphical representation.

PubMed Google ScholarContributionsVRP构思了这个项目并监督了这项研究。SSJ设计并进行了大多数实验，AP和PS进行了额外的研究。SSJ，AP和VRP在所有作者的投入下撰写了手稿。SSG，SSJ和AP进行了生物信息学分析，包括用于下游分析和图形表示的脚本。

SSJ, CA, and AP made and edited figures. SG performed histological characterization and provided histopathology images. JG and VKF contributed to breeding and maintaining the mouse colony.Corresponding authorCorrespondence to.

SSJ，CA和AP制作并编辑了数字。SG进行了组织学表征并提供了组织病理学图像。JG和VKF有助于繁殖和维持小鼠群体。对应作者对应。

Vikram R. Paralkar.Ethics declarations

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Reprints and permissionsAbout this articleCite this articleJalnapurkar, S.S., Pawar, A.S., George, S.S. et al. PHF6 suppresses self-renewal of leukemic stem cells in AML.

转载和许可本文引用本文Jalnapurkar，S.S.，Pawar，A.S.，George，S.S。等人。PHF6抑制AML中白血病干细胞的自我更新。

Leukemia (2024). https://doi.org/10.1038/s41375-024-02340-5Download citationReceived: 27 January 2024Revised: 26 June 2024Accepted: 03 July 2024Published: 14 July 2024DOI: https://doi.org/10.1038/s41375-024-02340-5Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

白血病（2024）。https://doi.org/10.1038/s41375-024-02340-5Download引文收到日期：2024年1月27日修订日期：2024年6月26日接受日期：2024年7月3日发布日期：2024年7月14日OI：https://doi.org/10.1038/s41375-024-02340-5Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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