Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
UCL Cancer Institute, University College London, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6BT, United Kingdom.
Nat Commun. 2022 Oct 3;13(1):5829. doi: 10.1038/s41467-022-33189-w.
Blood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events initiating abnormal growth ultimately determine the cancer subtype and subsequent clinical outcome. HOXA9 plays an important role in acute myeloid leukaemia (AML) prognosis by promoting blood cell expansion and altering differentiation; however, the function of HOXA9 in other blood malignancies is still unclear. Here, we highlight the biological switch and prognosis marker properties of HOXA9 in AML and chronic myeloproliferative neoplasms (MPN). First, we establish the ability of HOXA9 to stratify AML patients with distinct cellular and clinical outcomes. Then, through the use of a computational network model of MPN, we show that the self-activation of HOXA9 and its relationship to JAK2 and TET2 can explain the branching progression of JAK2/TET2 mutant MPN patients towards divergent clinical characteristics. Finally, we predict a connection between the RUNX1 and MYB genes and a suppressive role for the NOTCH pathway in MPN diseases.
血液恶性肿瘤是由于造血失调引起的。血细胞的类型和引发异常生长的特定致癌事件的顺序最终决定了癌症亚型和随后的临床结果。HOXA9 通过促进血细胞扩增和改变分化在急性髓性白血病 (AML) 预后中发挥重要作用；然而，HOXA9 在其他血液恶性肿瘤中的功能尚不清楚。在这里，我们强调了 HOXA9 在 AML 和慢性骨髓增生性肿瘤 (MPN) 中的生物学开关和预后标志物特性。首先，我们确定了 HOXA9 能够对具有不同细胞和临床结果的 AML 患者进行分层。然后，通过使用 MPN 的计算网络模型，我们表明 HOXA9 的自我激活及其与 JAK2 和 TET2 的关系可以解释 JAK2/TET2 突变 MPN 患者向不同临床特征的分支进展。最后，我们预测了 RUNX1 和 MYB 基因之间的联系以及 NOTCH 通路在 MPN 疾病中的抑制作用。
