Jaroslaw  Maciejewski,  M.D., Ph.D.

Jaroslaw Maciejewski, M.D., Ph.D.

Chair

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195
Location: -

Phone: (216) 445-5962
Fax: (216) 636-2498

 

Our group conducts translational investigations of the pathophysiology of bone marrow failure syndromes, including aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplastic syndromes, and related diseases. Aplastic anemia is a model of immune-mediated bone marrow failure syndromes and other immune cytopenias. Two aspects of this disease are the focus of our research: defective hematopoietic stem cell function, and its consequences and immune pathogenesis of stem-cell damage. Identification of expanded T-cell clones based on their unique TCR structure can also be applied to study anti-tumor immune surveillance such as that seen following allogeneic bone marrow transplantation in the form of the graft-versus-leukemia effect. We are also using similar principles to study clonal T-cell malignancies such as large granular lymphocyte leukemia, hairy cell leukemia, and T-cell lymphomas. Other ongoing studies include investigations of genetic predisposition and acquired chromosomal damage in myelodysplastic syndrome and acute myeloid leukemia using whole genome scanning approaches such as single nucleotide polymorphism arrays, methylation and expression arrays. These studies aim at development of novel molecular diagnostics and identification molecular targets for novel therapies.


Selected recent publications:

Adema V, Palomo L, Toma A, Kosmider O, Fuster-Tormo F, Benito R, Salgado R, Such E, Larrayoz MJ, Xicoy B, Hernandez-Sanchez JM, Maietta P, Neef A, Fontenay M, Ibañez M, Diez-Campelo M, Alvarez S, Maciejewski JP, Fenaux P, Sole F. Distinct mutational pattern of myelodysplastic syndromes with and without 5q-treated with lenalidomide. Br J Haematol. 2020 Mar 9. doi: 10.1111/bjh.16558.[Epub ahead of print] PubMed PMID: 32147816.

Gurnari C, Voso MT, Maciejewski JP, Visconte V. From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia. Cancers (Basel). 2020 Feb 4;12(2). pii: E357. doi: 10.3390/cancers12020357. Review. PubMed PMID: 32033196; PubMed Central PMCID: PMC7072629.

Patel BJ, Barot SV, Kuzmanovic T, Kerr C, Przychodzen BP, Thota S, Lee S, Patel S, Radivoyevitch T, Lichtin A, Advani A, Kalaycio M, Sekeres MA, Carraway HE, Maciejewski JP. Distinctive and common features of moderate aplastic anaemia. Br J Haematol. 2020 Jan 31. doi: 10.1111/bjh.16460. [Epub ahead of print] PubMed PMID: 32004386.

Awada H, Mahfouz RZ, Durrani J, Kishtagari A, Jagadeesh D, Lichtin AE, Hill BT, Hamilton BK, Carraway HE, Nazha A, Majhail NS, Sobecks R, Visconte V, Kalaycio M, Sekeres MA, Maciejewski JP. Large granular lymphocytic leukaemia after solid organ and haematopoietic stem cell transplantation. Br J Haematol. 2020 Apr;189(2):318-322. doi: 10.1111/bjh.16336. Epub 2020 Jan 20. PubMed PMID:31958160.

Patel BJ, Barot SV, Waldron M, Billings S, Vij A, Sekeres MA, Maciejewski JP, Carraway HE. Clonal dynamics of aplastic anemia/paroxysmal nocturnal hemoglobinuria. Leuk Lymphoma. 2020 May;61(5):1242-1245. doi: 10.1080/10428194.2019.1706734. Epub 2019 Dec 28. PubMed PMID: 31885297.

Saygin C, Kishtagari A, Cassaday RD, Reizine N, Yurkiewicz I, Liedtke M, Stock W, Larson RA, Levine RL, Tallman MS, Park JH, Kerr C, Przychodzen B, Sekeres MA, Kalaycio ME, Carraway HE, Hamilton BK, Sobecks R, Gerds A, Mukherjee S, Nazha A, Maciejewski JP, Advani AS. Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse genetic features and clinical outcomes. Blood Adv.2019 Dec 23;3(24):4228-4237. doi: 10.1182/bloodadvances.2019000925. PubMed PMID: 31869410; PubMed Central PMCID: PMC6929388.

Durrani J, Maciejewski JP. Idiopathic aplastic anemia vs hypocellular myelodysplastic syndrome. Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):97-104. doi: 10.1182/hematology.2019000019. PubMed PMID: 31808900; PubMed Central PMCID: PMC6913491.

Nagata Y, Makishima H, Kerr CM, Przychodzen BP, Aly M, Goyal A, Awada H, Asad MF, Kuzmanovic T, Suzuki H, Yoshizato T, Yoshida K, Chiba K, Tanaka H, Shiraishi Y, Miyano S, Mukherjee S, LaFramboise T, Nazha A, Sekeres MA, Radivoyevitch T, Haferlach T, Ogawa S, Maciejewski JP. Invariant patterns of clonal succession determine specific clinical features of myelodysplastic syndromes. Nat Commun. 2019 Nov 26;10(1):5386. doi: 10.1038/s41467-019-13001-y. PubMed PMID: 31772163; PubMed Central PMCID: PMC6879617.

Nagata Y, Maciejewski JP. The functional mechanisms of mutations in myelodysplastic syndrome. Leukemia. 2019 Dec;33(12):2779-2794. doi: 10.1038/s41375-019-0617-3. Epub 2019 Oct 31. Review. PubMed PMID: 31673113.

Nazha A, Sekeres MA, Bejar R, Rauh MJ, Othus M, Komrokji RS, Barnard J, Hilton CB, Kerr CM, Steensma DP, DeZern A, Roboz G, Garcia-Manero G, Erba H, Ebert BL, Maciejewski JP. Genomic Biomarkers to Predict Resistance to Hypomethylating Agents in Patients With Myelodysplastic Syndromes Using Artificial Intelligence. JCO Precis Oncol. 2019;3. doi: 10.1200/po.19.00119. Epub 2019 Sep 20. PubMed PMID: 31663066; PubMed Central PMCID: PMC6818517.

Durrani J, Awada H, Kishtagari A, Visconte V, Kerr C, Adema V, Nagata Y, Kuzmanovic T, Hong S, Patel B, Nazha A, Lichtin A, Mukherjee S, Saunthararajah Y, Carraway H, Sekeres M, Maciejewski JP. Large granular lymphocytic leukemia coexists with myeloid clones and myelodysplastic syndrome. Leukemia. 2020 Mar;34(3):957-962. doi: 10.1038/s41375-019-0601-y. Epub 2019 Oct 17. PubMed PMID:31624375.

Awada H, Rahman S, Durrani J, Asad MF, Kerr CM, Adema V, Kishtagari A, Graham A, Snider CA, Kongkiatkamon S, Nagata Y, Patel BJ, Carraway HE, Sekeres MA, Maciejewski JP, Visconte V. Leukemia evolving from paroxysmal nocturnal hemoglobinuria. Leukemia. 2020 Jan;34(1):327-330. doi: 10.1038/s41375-019-0555-0. Epub 2019 Aug 20. PubMed PMID: 31431736.

Aly M, Ramdzan ZM, Nagata Y, Balasubramanian SK, Hosono N, Makishima H, Visconte V, Kuzmanovic T, Adema V, Nazha A, Przychodzen BP, Kerr CM, Sekeres MA, Abazeed ME, Nepveu A, Maciejewski JP. Distinct clinical and biological implications of CUX1 in myeloid neoplasms. Blood Adv. 2019 Jul 23;3(14):2164-2178. doi: 10.1182/bloodadvances.2018028423. PubMed PMID: 31320321; PubMed Central PMCID: PMC6650742.

Kishtagari A, Jha BK, Maciejewski JP. TET2 mutations and clonal dynamics. Oncotarget. 2019 Mar 12;10(21):2010-2011. doi: 10.18632/oncotarget.26779. eCollection 2019 Mar 12. PubMed PMID: 31007843; PubMed Central PMCID: PMC6459340.

Kerr CM, Clemente MJ, Chomczynski PW, Przychodzen B, Nagata Y, Adema V, Visconte V, Lichtin AE, Mustjoki S, Radivoyevitch T, Sekeres MA, Maciejewski JP. Subclonal STAT3 mutations solidify clonal dominance. Blood Adv. 2019 Mar 26;3(6):917-921. doi: 10.1182/bloodadvances.2018027862. PubMed PMID: 30898763; PubMed Central PMCID: PMC6436009.

Shen W, Kerr CM, Przychozen B, Mahfouz RZ, LaFramboise T, Nagata Y, Hanna R, Radivoyevitch T, Nazha A, Sekeres MA, Maciejewski JP. Impact of germline CTC1 alterations on telomere length in acquired bone marrow failure. Br J Haematol. 2019 Jun;185(5):935-939. doi: 10.1111/bjh.15862. Epub 2019 Mar 19. PubMed PMID:30891747; PubMed Central PMCID: PMC6536344.

Awada H, Nagata Y, Goyal A, Asad MF, Patel B, Hirsch CM, Kuzmanovic T, Guan Y, Przychodzen BP, Aly M, Adema V, Shen W, Williams L, Nazha A, Abazeed ME, Sekeres MA, Radivoyevitch T, Haferlach T, Jha BK, Visconte V, Maciejewski JP. Invariant phenotype and molecular association of biallelic TET2 mutant myeloid neoplasia. Blood Adv. 2019 Feb 12;3(3):339-349. doi: 10.1182/bloodadvances.2018024216. PubMed PMID: 30709865; PubMed Central PMCID:PMC6373752.

Vatolin S, Radivoyevitch T, Maciejewski JP. New drugs for pharmacological extension of replicative life span in normal and progeroid cells. NPJ Aging Mech Dis. 2019 Jan 16;5:2. doi: 10.1038/s41514-018-0032-4. eCollection 2019. PubMed PMID: 30675378; PubMed Central PMCID: PMC6335401.

Abuhadra N, Mukherjee S, Al-Issa K, Adema V, Hirsch CM, Advani A, Przychodzen B, Makhoul A, Awada H, Maciejewski JP, Sekeres MA, Nazha A. BCOR and BCORL1 mutations in myelodysplastic syndromes (MDS): clonal architecture and impact on outcomes. Leuk Lymphoma. 2019  Jun;60(6):1587-1590. doi:  0.1080/10428194.2018.1543885. Epub 2019 Jan 8. PubMed PMID: 30618304.

Lee JW, Peffault de Latour R, Brodsky RA, Jang JH, Hill A, Röth A, Schrezenmeier H, Wilson A, Marantz JL, Maciejewski JP. Effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia in the International PNH Registry. Am J Hematol. 2019 Jan;94(1):E37-E41. doi: 10.1002/ajh.25334. Epub 2018 Nov 25. PubMed PMID: 30370949.


12/11/2020 |  

Cancer Researchers Identify Potential New Class of Drugs to Treat Blood and Bone Marrow Cancers

A new study by researchers in Cleveland Clinic’s Taussig Cancer and Lerner Research Institutes describes a novel class of targeted cancer drugs that may prove effective in treating certain common types of leukemia. The results first appeared online in Blood Cancer Discovery.