Rajewsky, K. Clonal selection and learning in the antibody system. Nature 381, 751–758 (1996).
Ehrlich, P. Die Schutzstoffe des Blutes. 73 Verh. Ges. Dtsch. Naturforsch. Aerzte 1, 250–275; English translation available in: Ehrlich, P. in Collected Studies on Immunity (ed. Bolduan, C.) 364–389 (Wiley, 1906).
Nossal, G. J. & Lederberg, J. Antibody production by single cells. Nature 181, 1419–1420 (1958).
Burnet, F. M. The Clonal Selection Theory of Acquired Immunity (Cambridge Univ. Press, 1959).
Pelanda, R. & Torres, R. M. Central B-cell tolerance: where selection begins. Cold Spring Harb. Perspect. Biol. 4, a007146 (2012).
Lam, K. P., Kühn, R. & Rajewsky, K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90, 1073–1083 (1997).
Kraus, M., Alimzhanov, M. B., Rajewsky, N. & Rajewsky, K. Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer. Cell 117, 787–800 (2004).
Srinivasan, L. et al. PI3 kinase signals BCR-dependent mature B cell survival. Cell 139, 573–586 (2009).
Nemazee, D. A. & Bürki, K. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature 337, 562–566 (1989).
Feldhahn, N. et al. Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic leukemia cells. J. Exp. Med. 201, 1837–1852 (2005).
Lee, H. et al. Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus. Mol. Cell. Biol. 9, 5219–5228 (1998).
Mancao, C. & Hammerschmidt, W. Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood 110, 3715–3721 (2007).
Jain, M. et al. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science. 297, 102–104 (2002).
Weinstein, I. B. Addiction to oncogenes — the Achilles heal of cancer. Science 297, 63–64 (2002).
Davis, R. E. et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463, 88–92 (2010).
Schmitz, R. et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature 490, 116–120 (2012).
Chen, L. et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 111, 2230–2237 (2008).
Byrd, J. C. et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 369, 32–42 (2013).
Wang, M. L. et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N. Engl. J. Med. 369, 507–516 (2013).
Gopal, A. K. et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N. Engl. J. Med. 370, 1008–1018 (2014).
Chen, Z. et al. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukemia. Nature 521, 357–361 (2015).
Shojaee, S. et al. PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nat. Med. 22, 379–387 (2016).
Shojaee, S. et al. Erk negative feedback control enables pre-B cell transformation and represents a therapeutic target in acute lymphoblastic leukemia. Cancer Cell 28, 114–128 (2015).
Sakaguchi, N. & Melchers, F. Lambda 5, a new light-chain-related locus selectively expressed in pre-B lymphocytes. Nature 324, 579–582 (1986).
Ohnishi, K. & Melchers, F. The nonimmunoglobulin portion of lambda5 mediates cell-autonomous pre-B cell receptor signaling. Nat. Immunol. 9, 849–856 (2003).
Ubelhart, R. et al. N-linked glycosylation selectively regulates autonomous precursor BCR function. Nat. Immunol. 8, 759–765 (2010).
Ippolito, G. C. et al. Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production. J. Exp. Med. 203, 1567–1578 (2006).
Minegishi, Y. & Conley, M. E. Negative selection at the pre-BCR checkpoint elicited by human mu heavy chains with unusual CDR3 regions. Immunity 14, 631–641 (2001).
Keenan, R. A. et al. Censoring of autoreactive B cell development by the pre-B cell receptor. Science 321, 696–699 (2008).
Ren, W. et al. Surrogate light chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by marginal zone B cells. Eur. J. Immunol. 4, 1228–1237.
Grimsholm, O. et al. Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells. Nat. Commun. 6, 7077 (2015).
Tiegs, S. L., Russell, D. M. & Nemazee, D. Receptor editing in self-reactive bone marrow B. cells. J. Exp. Med. 177, 1009–1020 (1993).
Wardemann, H. et al. Predominant autoantibody production by early human B cell precursors. Science 301, 1374–1377 (2003).
Reth, M. Antigen receptor tail clue. Nature 338, 383–384 (1989).
Saijo, K. et al. Essential role of Src-family protein tyrosine kinases in NF-κB activation during B cell development. Nat. Immunol. 4, 274–279 (2003).
Turner, M. et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378, 298–302 (1995).
Hata, A., Sabe, H., Kurosaki, T., Takata, M. & Hanafusa, H. Functional analysis of Csk in signal transduction through the B-cell antigen receptor. Mol. Cell. Biol. 11, 7306–7313 (1994).
Sieh, M., Bolen, J. B. & Weiss, A. CD45 specifically modulates binding of Lck to a phosphopeptide encompassing the negative regulatory tyrosine of Lck. EMBO J 12, 315–321 (1993).
Kurosaki, T. et al. Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling. J. Exp. Med. 179, 1725–1729 (1994).
Rolli, V. et al. Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol. Cell 5, 1057–1069 (2002).
Königsberger, S. et al. Altered BCR signalling quality predisposes to autoimmune disease and a pre-diabetic state. EMBO J. 31, 3363–3374 (2012).
Kersseboom, R. et al. Bruton's tyrosine kinase cooperates with the B cell linker protein SLP-65 as a tumor suppressor in Pre-B cells. J. Exp. Med. 198, 91–98 (2003).
Feldhahn, N. et al. Deficiency of Bruton's tyrosine kinase in B cell precursor leukemia cells. Proc. Natl Acad. Sci. USA 102, 13266–13271 (2005).
Jumaa, H. et al. Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65. Immunity 11, 547–554 (1999).
Egawa, T. et al. Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation. Curr. Biol. 13, 1252–1258 (2003).
Hashimoto, A. et al. Involvement of guanosine triphosphatases and phospholipase C-gamma2 in extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase activation by the B cell antigen receptor. J. Exp. Med. 188, 1287–1295 (1998).
Clynes, R. et al. Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J. Exp. Med. 189, 179–185 (1999).
Yurasov, S. et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J. Exp. Med. 201, 703–711 (2005).
Samuels, J., Ng, Y. S., Coupillaud, C., Paget, D. & Meffre, E. Impaired early B cell tolerance in patients with rheumatoid arthritis. J. Exp. Med. 201, 1659–1667 (2005).
Ramadani, F. et al. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci. Signal. 3, ra60 (2010).
O'Neill, S. K. et al. Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy. Immunity 35, 746–756.
Suzuki, A. et al. Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. J. Exp. Med. 197, 657–667 (2003).
Deau, M. C. et al. A human immunodeficiency caused by mutations in the PIK3R1 gene. J. Clin. Invest. 124, 3923–3928.
Cheng, S. et al. BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten. Cell Res. 19, 196–207.
Rowland, S. L., DePersis, C. L., Torres, R. M. & Pelanda, R. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J. Exp. Med. 207, 607–621 (2010).
Mandal, M. et al. Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development. Nat. Immunol. 10, 1110–1117 (2010).
Yasuda, T. et al. Erk kinases link pre-B cell receptor signaling to transcriptional events required for early B cell expansion. Immunity 28, 499–508 (2008).
Anderson, L. J. & Longnecker, R. EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway. J. Gen. Virol. 89, 1563–1568 (2008).
Teodorovic, L. S. et al. Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies. Proc. Natl Acad. Sci. USA 111, E2797–E2806 (2014).
Limnander, A. et al. STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development. Nat. Immunol. 12, 425–433 (2011).
Guilbault, B. & Kay, R. J. RasGRP1 sensitizes an immature B cell line to antigen receptor-induced apoptosis. J. Biol. Chem. 279, 19523–19530 (2004).
Mecklenbrauker, I., Saijo, K., Zheng, N. Y., Leitges, M. & Tarakhovsky, A. Protein kinase Cδ controls self-antigen-induced B-cell tolerance. Nature 416, 860–865 (2002).
Stang, S. L. et al. A proapoptotic signaling pathway involving RasGRP, Erk, and Bim in B cells. Exp. Hematol. 37, 122–134 (2009).
Enders, A. et al. Loss of the proapoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. J. Exp. Med. 198, 1119–1126 (2003).
Luciano, F. et al. Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene 22, 6785–6793 (2003).
Ley, R., Balmanno, K., Hadfield, K., Weston, C. & Cook, S. J. Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein Bim. J. Biol. Chem. 278, 18811–18816 (2003).
Turner, M. et al. Syk tyrosine kinase is required for the positive selection of immature B cells into the recirculating B cell pool. J. Exp. Med. 186, 2013–2021 (1997).
Pan, C., Baumgarth, N. & Parnes, J. R. CD72-deficient mice reveal nonredundant roles of CD72 in B cell development and activation. Immunity 11, 495–506 (1999).
Gurung, P. et al. Tyrosine kinase SYK licenses MyD88 adaptor protein to instigate IL-1α-mediated inflammatory disease. Immunity 46, 635–648 (2017).
Rickard, J. A. et al. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157, 1175–1188 (2014).
Latour, S., Zhang, J., Siraganian, R. P. & Veillette, A. A unique insert in the linker domain of Syk is necessary for its function in immunoreceptor signaling. EMBO J. 17, 2584–2595 (1998).
Chen, L. et al. Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood 100, 4609–4614 (2002).
Getahun, A., Beavers, N. A., Larson, S. R., Shlomchik, M. J. & Cambier, J. C. Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells. J. Exp. Med. 213, 751–769 (2006).
Hug, E., Hobeika, E., Reth, M. & Jumaa, H. Inducible expression of hyperactive Syk in B cells activates Blimp-1-dependent terminal differentiation. Oncogene 33, 3730–3741.
Kersseboom, R. et al. Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells. Eur. J. Immunol. 40, 2643–2654.
Hoyer, B. F. et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J. Exp. Med. 199, 1577–1584 (2004).
Bailet, O. et al. Spleen tyrosine kinase functions as a tumor suppressor in melanoma cells by inducing senescence-like growth arrest. Cancer Res. 69, 2748–2756 (2009).
Collado, M. et al. Tumour biology: senescence in premalignant tumours. Nature 436, 642 (2005).
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997).
Alimonti, A. et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J. Clin. Invest. 120, 681–693 (2010).
Di Micco, R. et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444, 638–642 (2006).
Rocha, B. & von Boehmer, H. Peripheral selection of the T cell repertoire. Science 251, 1225–1228 (1991).
Guo, W. et al. Multi-genetic events collaboratively contribute to Pten-null leukemia stem-cell formation. Nature 453, 529–533.
Tretter, T., Ross, A. E., Dordai, D. I. & Desiderio, S. Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk. J. Exp. Med. 198, 1863–1873 (2003).
Klein, F. et al. The BCR-ABL1 kinase bypasses selection for the expression of a pre-B cell receptor in pre-B acute lymphoblastic leukemia cells. J. Exp. Med. 199, 673–685 (2004).
Merchant, M., Caldwell, R. G. & Longnecker, R. The LMP2A ITAM is essential for providing B cells with development and survival signals in vivo. J. Virol. 74, 9115–9124 (2000).
Lee, B. S., Alvarez, X., Ishido, S., Lackner, A. A. & Jung, J. U. Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1. J. Exp. Med. 192, 11–21 (2000).
Young, R. M. & Staudt, L. M. Targeting pathological B cell receptor signalling in lymphoid malignancies. Nat. Rev. Drug Discov. 12, 229–243 (2013).
Müschen, M. Rationale for targeting the pre-B-cell receptor signaling pathway in acute lymphoblastic leukemia. Blood 125, 3688–3693 (2015).
Erasmus, M. F. et al. Dynamic pre-BCR homodimers fine-tune autonomous survival signals in B cell precursor acute lymphoblastic leukemia. Sci. Signal. 9, ra116 (2016).
Geng, H. et al. Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia. Cancer Cell. 27, 409–425 (2015).
Trageser, D. et al. Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function. J. Exp. Med. 206, 1739–1753 (2009).
Chan, L. N. et al. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature 542, 479–483 (2017).
Mangum, D. S. et al. VPREB1 deletions occur independent of lambda light chain rearrangement in childhood acute lymphoblastic leukemia. Leukemia 28, 216–220 (2014).
Jumaa, H. et al. Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukemia. Nature 423, 452–456 (2003).
Sprangers, M. et al. SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells. Oncogene 25, 5180–5186 (2006).
Roberts, K. G. et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N. Engl. J. Med. 371, 1005–1015 (2014).
Zhang, J. et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 118, 3080–3087 (2011).
Irving, J. et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood 124, 3420–3430 (2014).
Bräuninger, A. et al. Survival and clonal expansion of mutating “forbidden” (immunoglobulin receptor-deficient) Epstein-Barr virus-infected B cells in angioimmunoblastic T cell lymphoma. J. Exp. Med. 194, 927–940 (2001).
Kanzler, H., Küppers, R., Hansmann, M. L. & Rajewsky, K. Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J. Exp. Med. 184, 1495–1505 (1996).
Lu, P. et al. Early events of B-cell receptor signaling are not essential for the proliferation and viability of AIDS-related lymphoma. Leukemia 23, 807–810 (2009).
Brauninger, A. et al. Epstein-Barr virus (EBV)-positive lymphoproliferations in post-transplant patients show immunoglobulin V gene mutation patterns suggesting interference of EBV with normal B cell differentiation processes. Eur. J. Immunol. 33, 1593–1602 (2003).
Savage, K. J. et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 102, 3871–3879 (2003).
Jungnickel, B. et al. Clonal deleterious mutations in the IKBA gene in the malignant cells in Hodgkin's lymphoma. J. Exp. Med. 191, 395–402 (2000).
Schmitz, R. et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J. Exp. Med. 206, 981–989 (2009).
Lenz, G. et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319, 1676–1679 (2008).
Ngo, V. N. et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 470, 115–119 (2011).
Joos, S. et al. Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells. Cancer Res. 60, 549–552 (2000).
Melzner, I. et al. Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line. Blood 105, 2535–2542 (2005).
Mottok, A. et al. Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities. Blood 114, 4503–4506 (2009).
Nagel, P. D. et al. KIT mutations in primary mediastinal B-cell lymphoma. Blood Cancer J. 4, e241 (2014).
Mancao, C. et al. Rescue of “crippled” germinal center B cells from apoptosis by Epstein-Barr virus. Blood 106, 4339–4344 (2005).
Bechtel, D. et al. Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood 106, 4345–4350 (2005).
Asahi, M. et al. Helicobacter pylori CagA containing ITAM-like sequences localized to lipid rafts negatively regulates VacA-induced signaling in vivo. Helicobacter 8, 1–14 (2003).
Krysiak, K. et al. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood 129, 473–483 (2017).
Smeenk, L. et al. Molecular role of the PAX5-ETV6 oncoprotein in promoting B-cell acute lymphoblastic leukemia. EMBO J. 36, 718–735.
Hoogeboom, R. et al. A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J. Exp. Med. 210, 59–70.
Quinn, E. R. et al. The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis. Blood 98, 3745–3749 (2001).
Parsonnet, J. et al. Helicobacter pylori infection and gastric lymphoma. N. Engl. J. Med. 330, 1267–1271 (1994).
Robbiani, D. F. et al. Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma. Cell 162, 727–737 (2015).
Dühren-von Minden, M. et al. Chronic lymphocytic leukemia is driven by antigen independent cell-autonomous signalling. Nature 489, 309–312 (2012).
Minici, C. et al. Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukemia. Nat. Commun. 8, 15746 (2017).
Tiacci, E. et al. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N. Engl. J. Med. 373, 1733–1747 (2015).
Kuil, J., Fischer, M. J., de Mol, N. J. & Liskamp, R. M. Cell permeable ITAM constructs for the modulation of mediator release in mast cells. Org. Biomol. Chem. 9, 820–833 (2011).
Pracht, C., Minguet, S., Leitges, M., Reth, M. & Huber, M. Association of protein kinase C-delta with the B cell antigen receptor complex. Cell Signal. 19, 715–722 (2007).
Limnander, A. et al. Protein kinase Cδ promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance. Mol. Cell. Biol. 34, 1474–1485 (2014).
Bhavanasi, D., Kostyak, J. C., Swindle, J., Kilpatrick, L. E. & Kunapuli, S. P. CGX1037 is a novel PKC isoform delta selective inhibitor in platelets. Platelets 26, 2–9 (2015).
Pathak, M. K. & Yi, T. Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines. J. Immunol. 167, 3391–3397 (2001).
Brooks, R. et al. SHIP1 inhibition increases immunoregulatory capacity and triggers apoptosis of hematopoietic cancer cells. J. Immunol. 184, 3582–3589 (2010).
Srivastava, N. et al. A small-molecule inhibitor of SHIP1 reverses age- and diet-associated obesity and metabolic syndrome. JCI Insight 1, e88544 (2016).
Vang, T. et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat. Genet. 37, 1317–1319 (2005).
Negro, R. et al. Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated CLL cells by selectively activating AKT. Blood 119, 6278–6287 (2012).
Hebbring, S. J. et al. Genetic evidence of PTPN22 effects on chronic lymphocytic leukemia. Blood 121, 237–238 (2013).
Schickel, J.-N. et al. PTPN22 inhibition resets defective human central B cell tolerance. Sci. Immunol. 1, aaf7153 (2016).
Vang, T. et al. LYP inhibits T-cell activation when dissociated from CSK. Nat. Chem. Biol. 8, 437–446 (2012).
Li, J. et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943–1947 (1997).
Li, Y. et al. Pretreatment with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor SF1670 augments the efficacy of granulocyte transfusion in a clinically relevant mouse model. Blood 117, 6702–6713 (2011).
Jo, H. et al. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc. Natl Acad. Sci. USA 109, 10581–10586 (2012).
Molina, G. et al. Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat. Chem. Biol. 5, 680–687 (2009).
Hong, C. S. et al. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential. Cancer Biol. Ther. 16, 821–833 (2015).
Iwama, Y. & Eguchi, M. Quantitative evaluation of leukemic mitochondria with a computer-controlled image analyzer. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 51, 375–384 (1986).
Kaspers, G. J. et al. Different cellular drug resistance profiles in childhood lymphoblastic and non-lymphoblastic leukemia: a preliminary report. Leukemia 8, 1224–1229 (1994).
Druker, B. J. et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. 344, 1038–1042 (2001).
Zabriskie, M. S. et al. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell. 26, 428–442 (2014).
Schwartzman, O. et al. Suppressors and activators of JAK-STAT signaling at diagnosis and relapse of acute lymphoblastic leukemia in Down syndrome. Proc. Natl Acad. Sci. USA 114, E4030–E4039 (2017).
Jones, C. L. et al. MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia. Blood 126, 2202–2212 (2015).
Hardy, R. R. & Hayakawa, K. B cell development pathways. Annu. Rev. Immunol. 19, 595–621 (2001).